Context Navigation

← Previous Ticket
Next Ticket →

#16580 closed defect (fixed)

Memory leak

Reported by:	Tristan Croll	Owned by:	Eric Pettersen
Priority:	normal	Milestone:
Component:	Performance	Version:
Keywords:		Cc:	chimera-programmers
Blocked By:		Blocking:
Notify when closed:		Platform:	all
Project:	ChimeraX

Description (last modified by Eric Pettersen)

The following bug report has been submitted:
Platform:        Linux-6.8.0-49-generic-x86_64-with-glibc2.35
ChimeraX Version: 1.9 (2024-12-11 19:11:19 UTC)
Description
Long-running session working with ISOLDE has chewed up almost all of my system memory. Trying a few things with tracemalloc running, it looks like there's a memory leak in the ribbon code (see below). Can't seem to replicate this on my Windows machine so far, and can't do much more with this session without freezing up my Linux box entirely. Will test again in a fresh session.

import tracemalloc
tracemalloc.start()
before = tracemalloc.take_snapshot()
# run and stop a few ISOLDE simulations

after = tracemalloc.take_snapshot()

top_stats = after.compare_to(before, 'lineno')

for stat in top_stats[:10]:
    print(stat)
/usr/lib/ucsf-chimerax/lib/python3.11/site-packages/chimerax/atomic/ribbon.py:542: size=259 MiB (+259 MiB), count=60 (+60), average=4412 KiB
/usr/lib/ucsf-chimerax/lib/python3.11/site-packages/chimerax/graphics/opengl.py:2826: size=23.5 MiB (+23.5 MiB), count=50 (+50), average=480 KiB
/usr/lib/ucsf-chimerax/lib/python3.11/site-packages/chimerax/atomic/ribbon.py:651: size=22.8 MiB (+22.8 MiB), count=22 (+22), average=1063 KiB
/usr/lib/ucsf-chimerax/lib/python3.11/site-packages/chimerax/atomic/molarray.py:1005: size=6469 KiB (+6469 KiB), count=17 (+17), average=381 KiB
/usr/lib/ucsf-chimerax/lib/python3.11/site-packages/chimerax/atomic/structure.py:2411: size=3448 KiB (+3448 KiB), count=20 (+20), average=172 KiB
/usr/lib/ucsf-chimerax/lib/python3.11/site-packages/chimerax/atomic/molarray.py:378: size=2880 KiB (+2880 KiB), count=74 (+74), average=38.9 KiB
/usr/lib/ucsf-chimerax/lib/python3.11/site-packages/chimerax/atomic/molc.py:207: size=2130 KiB (+2130 KiB), count=288 (+288), average=7572 B
/usr/lib/ucsf-chimerax/lib/python3.11/site-packages/chimerax/atomic/molarray.py:366: size=2106 KiB (+2106 KiB), count=72 (+72), average=29.2 KiB
/usr/lib/ucsf-chimerax/lib/python3.11/site-packages/chimerax/atomic/ribbon.py:676: size=1985 KiB (+1985 KiB), count=2 (+2), average=992 KiB
/usr/lib/ucsf-chimerax/lib/python3.11/site-packages/chimerax/atomic/structure.py:419: size=1870 KiB (+1870 KiB), count=22 (+22), average=85.0 KiB

Log:
Startup Messages  
---  
note | available bundle cache has not been initialized yet  
  
You can double click a model's Name or ID in the model panel to edit those
fields  

> isolde shorthand
    
    
    Initialising ISOLDE-specific command aliases:
    Alias	Equivalent full command
    -------------------------------------------------
    st	isolde step {arguments}
    aw	isolde add water {arguments}
    awsf	isolde add water {arguments} sim false
    al	isolde add ligand {arguments}
    aa	isolde add aa $1 sel {arguments}
    ht	isolde mod his sel {arguments}
    so	setattr sel atoms occupancy {arguments}
    ab	isolde adjust bfactors {arguments}
    ss	isolde sim start sel
    rt	isolde release torsions sel {arguments}
    rd	isolde release distances sel {arguments}
    ra	rd; rt
    pf	isolde pepflip sel
    cf	isolde cisflip sel
    cbb	color bfactor {arguments}
    cbo	color byattr occupancy {arguments}
    cbc	color {arguments} bychain; color {arguments} byhet
    cs	clipper set contourSensitivity {arguments}
    

  
UCSF ChimeraX version: 1.9 (2024-12-11)  
© 2016-2024 Regents of the University of California. All rights reserved.  
How to cite UCSF ChimeraX  

> open 9ce3

Summary of feedback from opening 9ce3 fetched from pdb  
---  
note | Fetching compressed mmCIF 9ce3 from http://files.rcsb.org/download/9ce3.cif  
  
9ce3 title:  
Structure of the TSC:WIPI3 lysosomal recruitment complex [more info...]  
  
Chain information for 9ce3 #1  
---  
Chain | Description | UniProt  
A B | Isoform 4 of Tuberin | TSC2_HUMAN 2-1807  
C D | Hamartin | TSC1_HUMAN 1-1164  
E | TBC1 domain family member 7 | TBCD7_HUMAN 1-293  
F | WD repeat domain phosphoinositide-interacting protein 3 | WIPI3_HUMAN 12-320  
G H | Unknown fragment |   
  

> log metadata #1

Metadata for 9ce3 #1  
---  
Title | Structure of the TSC:WIPI3 lysosomal recruitment complex  
Citation | Bayly-Jones, C., Lupton, C.J., D'Andrea, L., Chang, Y.G., Jones, G.D., Steele, J.R., Venugopal, H., Schittenhelm, R.B., Halls, M.L., Ellisdon, A.M. (2024). Structure of the human TSC:WIPI3 lysosomal recruitment complex. Sci Adv, 10, eadr5807-eadr5807. PMID: 39565846. DOI: 10.1126/sciadv.adr5807  
Source (natural) | Homo sapiens (human)  
Gene source | Homo sapiens (human)  
CryoEM Map | EMDB 45492 — open map  
Experimental method | Electron microscopy  
Resolution | 2.9Å  
  
> open 45492 fromDatabase emdb

Summary of feedback from opening 45492 fetched from emdb  
---  
notes | Fetching compressed map 45492 from ftp://ftp.ebi.ac.uk/pub/databases/emdb/structures/EMD-45492/map/emd_45492.map.gz  
Fetching map header 45492 from
ftp://ftp.ebi.ac.uk/pub/databases/emdb/structures/EMD-45492/header/emd-45492.xml  
  
Opened emdb 45492 as #2, grid size 560,560,560, pixel 1.17, shown at level
0.05, step 4, values float32, fit PDB 9ce3  

> clipper associate #2 toModel #1

Opened emdb 45492 as #1.1.1.1, grid size 560,560,560, pixel 1.17, shown at
level 0.271, step 1, values float32  
9ce3 title:  
Structure of the TSC:WIPI3 lysosomal recruitment complex [more info...]  
  
Chain information for 9ce3  
---  
Chain | Description | UniProt  
1.2/A 1.2/B | Isoform 4 of Tuberin | TSC2_HUMAN 2-1807  
1.2/C 1.2/D | Hamartin | TSC1_HUMAN 1-1164  
1.2/E | TBC1 domain family member 7 | TBCD7_HUMAN 1-293  
1.2/F | WD repeat domain phosphoinositide-interacting protein 3 | WIPI3_HUMAN 12-320  
1.2/G 1.2/H | Unknown fragment |   
  

> addh

Summary of feedback from adding hydrogens to 9ce3 #1.2  
---  
warnings | Not adding hydrogens to /B ARG 418 CB because it is missing heavy-atom bond partners  
Not adding hydrogens to /B ARG 537 CB because it is missing heavy-atom bond
partners  
Not adding hydrogens to /D SER 871 CB because it is missing heavy-atom bond
partners  
Not adding hydrogens to /G UNK 1 CB because it is missing heavy-atom bond
partners  
Not adding hydrogens to /G UNK 2 CB because it is missing heavy-atom bond
partners  
22 messages similar to the above omitted  
notes | Termini for 9ce3 (#1.2) chain A determined from SEQRES records  
Termini for 9ce3 (#1.2) chain B determined from SEQRES records  
Termini for 9ce3 (#1.2) chain C determined from SEQRES records  
Termini for 9ce3 (#1.2) chain D determined from SEQRES records  
Termini for 9ce3 (#1.2) chain E determined from SEQRES records  
3 messages similar to the above omitted  
Chain-initial residues that are actual N termini: /G UNK 1, /H UNK 1  
Chain-initial residues that are not actual N termini: /A GLN 35, /A PRO 542,
/A ALA 678, /A ASP 1004, /A ASN 1182, /A GLU 1490, /B THR 41, /B GLY 676, /B
PRO 928, /B ASP 1004, /B ASN 1182, /B GLU 1490, /C ASN 6, /C SER 598, /C LEU
652, /D ASN 6, /D THR 615, /D PRO 645, /D ILE 688, /D GLU 839, /E GLY 18, /F
HIS 11  
Chain-final residues that are actual C termini: /G UNK 12, /H UNK 12  
Chain-final residues that are not actual C termini: /A ARG 537, /A ARG 653, /A
SER 937, /A LEU 1083, /A ALA 1248, /A ASN 1762, /B GLU 652, /B SER 923, /B SER
937, /B LEU 1083, /B ARG 1240, /B ASN 1762, /C SER 276, /C ARG 622, /C LYS
971, /D ASP 265, /D GLY 633, /D SER 671, /D VAL 831, /D LEU 969, /E SER 293,
/F MET 315  
Missing OXT added to C-terminal residue /G UNK 12  
Missing OXT added to C-terminal residue /H UNK 12  
4513 hydrogen bonds  
Adding 'H' to /A GLN 35  
Adding 'H' to /A ALA 678  
Adding 'H' to /A ASP 1004  
Adding 'H' to /A ASN 1182  
Adding 'H' to /A GLU 1490  
14 messages similar to the above omitted  
/A ASN 1762 is not terminus, removing H atom from 'C'  
/B ASN 1762 is not terminus, removing H atom from 'C'  
/C LYS 971 is not terminus, removing H atom from 'C'  
/D LEU 969 is not terminus, removing H atom from 'C'  
/E SER 293 is not terminus, removing H atom from 'C'  
1 messages similar to the above omitted  
35482 hydrogens added  
  

> isolde select #1

> set selectionWidth 4

ISOLDE: Checking and correcting nomenclature for (pseudo)symmetric side
chains...  
ISOLDE: Corrected atom nomenclature of 251 residues in model #1.2 to IUPAC-IUB
standards.  
Done loading forcefield  

> isolde set simFidelityMode Highest/Slowest

ISOLDE: setting sim fidelity mode to Highest/Slowest  
nonbonded_cutoff_distance = 1.700000  
use_gbsa = True  
gbsa_cutoff = 2.000000  

> alphafold match #1 trim false

Fetching AlphaFold database settings from
https://www.rbvi.ucsf.edu/chimerax/data/status/alphafold_database3.json  
Fetching compressed AlphaFold P49815 from
https://alphafold.ebi.ac.uk/files/AF-P49815-F1-model_v4.cif  
Fetching compressed AlphaFold Q92574 from
https://alphafold.ebi.ac.uk/files/AF-Q92574-F1-model_v4.cif  
Fetching compressed AlphaFold Q9P0N9 from
https://alphafold.ebi.ac.uk/files/AF-Q9P0N9-F1-model_v4.cif  
Fetching compressed AlphaFold Q5MNZ6 from
https://alphafold.ebi.ac.uk/files/AF-Q5MNZ6-F1-model_v4.cif  
4 AlphaFold models found using UniProt identifiers: P49815 (chains A,B),
Q92574 (chains C,D), Q9P0N9 (chain E), Q5MNZ6 (chain F)  

Cannot search short sequences less than 20 amino acids  

No AlphaFold model with similar sequence for chains G,H  

AlphaFold prediction matching 9ce3  
---  
Chain| UniProt Id| UniProt Name| RMSD| Length| Seen| % Id  
A | P49815 | TSC2_HUMAN | 8.04 | 1807 | 1295 | 100   
B | P49815 | TSC2_HUMAN | 6.80 | 1807 | 1282 | 100   
F | Q5MNZ6 | WIPI3_HUMAN | 1.51 | 344 | 305 | 98   
C | Q92574 | TSC1_HUMAN | 88.43 | 1164 | 616 | 100   
D | Q92574 | TSC1_HUMAN | 80.29 | 1164 | 581 | 100   
E | Q9P0N9 | TBCD7_HUMAN | 0.76 | 293 | 276 | 100   
  
Opened 6 AlphaFold models  

> matchmaker #2.1 to #1.2

Computing secondary structure  
[Repeated 1 time(s)]  Parameters  
---  
Chain pairing | bb  
Alignment algorithm | Needleman-Wunsch  
Similarity matrix | BLOSUM-62  
SS fraction | 0.3  
Gap open (HH/SS/other) | 18/18/6  
Gap extend | 1  
SS matrix |  |  | H | S | O  
---|---|---|---  
H | 6 | -9 | -6  
S |  | 6 | -6  
O |  |  | 4  
Iteration cutoff | 2  
  
Matchmaker 9ce3, chain B (#1.2) with AlphaFold TSC2_HUMAN chain A, chain A
(#2.1), sequence alignment score = 8146.5  
RMSD between 235 pruned atom pairs is 0.911 angstroms; (across all 1282 pairs:
6.796)  
  

> color #2.1 bychain

> color #2.1 byhetero

> color modify #2.1 hue + 50

ISOLDE: attempting to load PAE matrix for model #2.1 from the AlphaFold-EBI
database. If this fails or you wish to use a different PAE matrix, use the
"Load PAE matrix" button in ISOLDE's reference model restraints widget.  

> alphafold pae #2.1 uniprotId P49815 plot false

Fetching compressed AlphaFold PAE P49815 from
https://alphafold.ebi.ac.uk/files/AF-P49815-F1-predicted_aligned_error_v4.json  
Computing secondary structure  
[Repeated 1 time(s)]s1:
MDYKDDDDKAKPTSKDSGLKEKFKILLGLGTPRPNPRSAEGKQTEFIITAEILRELSMECGLNNRIRMIGQICEVAKTKKFEEHAVEALWKAVADLLQPERPLEARHAVLALLKAIVQGQGERLGVLRALFFKVIKDYPSNEDLHERLEVFKALTDNGRHITYLEEELADFVLQWMDVGLSSEFLLVLVNLVKFNSCYLDEYIARMVQMICLLCVRTASSVDIEVSLQVLDAVVCYNCLPAESLPLFIVTLCRTINVKELCEPCWKLMRNLLGTHLGHSAIYNMCHLMEDRAYMEDAPLLRGAVFFVGMALWGAHRLYSLRNSPTSVLPSFYQAMACPNEVVSYEIVLSITRLIKKYRKELQVVAWDILLNIIERLLQQLQTLDSPELRTIVHDLLTTVEELCDQNEFHGSQERYFELVERCADQRPESSLLNLISYRAQSIHPAKDGWIQNLQALMERFFRSESRGAVRIKVLDVLSFVLLINRQFYEEELINSVVISQLSHIPEDKDHQVRKLATQLLVDLAEGCHTHHFNSLLDIIEKVMARSLSPPPELEERDVAAYSASLEDVKTAVLGLLVILQTKLYTLPASHATRVYEMLVSHIQLHYKHSYTLPIASSIRLQAFDFLLLLRADSLHRLGLPNKDGVVRFSPYCVCDYMEPERGSEKKTSGPLSPPTGPPGPAPAGPAVRLGSVPYSLLFRVLLQCLKQESDWKVLKLVLGRLPESLRYKVLIFTSPCSVDQLCSALCSMLSGPKTLERLRGAPEGFSRTDLHLAVVPVLTALISYHNYLDKTKQREMVYCLEQGLIHRCASQCVVALSICSVEMPDIIIKALPVLVVKLTHISATASMAVPLLEFLSTLARLPHLYRNFAAEQYASVFAISLPYTNPSKFNQYIVCLAHHVIAMWFIRCRLPFRKDFVPFITKGLRSNVLLSFDDTPEKDSFRARSTSLNERPKSLRIARPPKQGLNNSPPVKEFKESSAAEAFRCRSISVSEHVVRSRIQTSLTSASLGSADENSVAQADDSLKNLHLELTETCLDMMARYVFSNFTAVPKRSPVGEFLLAGGRTKTWLVGNKLVTVTTSVGTGTRSLLGLDSGELQSGPESSSSPGVHVRQTKEAPAKLESQAGQQVSRGARDRVRSMSGGHGLRVGALDVPASQFLGSATSPGPRTAPAAKPEKASAGTRVPVQEKTNLAAYVPLLTQGWAEILVRRPTGNTSWLMSLENPLSPFSSDINNMPLQELSNALMAAERFKEHRDTALYKSLSVPAASTAKPPPLPRSNT.......................DSAVVMEEGSPGEVPVLVEPPGLEDVEAALGMDRRTDAYSRSSSVSSQEEKSLHAEELVGRGIPIERVVSSEGGRPSVDLSFQPSQPLSKSSSSPELQTLQDILGDPGDKADVGRLSPEVKARSQSGTLDGESAAWSASGEDSRGQPEGPLPSSSPRSPSGLRPRGYTISDSAPSRRGKRVERDALKSRATASNAEKVPGINPSFVFLQLYHSPFFGDESNKPILLPNESQSFERSVQLLDQIPSYDTHKIAVLYVGEGQSNSELAILSNEHGSYRYTEFLTGLGRLIELKDCQPDKVYLGGLDVCGEDGQFTYCWHDDIMQAVFHIATLMPTKDVDKHRCDKKRHLGNDFVSIVYNDSGEDFKLGTIKGQFNFVHVIVTPLDYECNLVSLQCRKDMEGLVDTSVAKIVSDRNLPFVARQMALHANMASQVHHSRSNPTDIYPSKWIARLRHIKRLRQRICEEAAYSNPSLPLVHPPSHSKAPAQTPAEPTPGYEVGQRKRLISSVEDFTEFV  
s2:
........MAKPTSKDSGLKEKFKILLGLGTPRPNPRSAEGKQTEFIITAEILRELSMECGLNNRIRMIGQICEVAKTKKFEEHAVEALWKAVADLLQPERPLEARHAVLALLKAIVQGQGERLGVLRALFFKVIKDYPSNEDLHERLEVFKALTDNGRHITYLEEELADFVLQWMDVGLSSEFLLVLVNLVKFNSCYLDEYIARMVQMICLLCVRTASSVDIEVSLQVLDAVVCYNCLPAESLPLFIVTLCRTINVKELCEPCWKLMRNLLGTHLGHSAIYNMCHLMEDRAYMEDAPLLRGAVFFVGMALWGAHRLYSLRNSPTSVLPSFYQAMACPNEVVSYEIVLSITRLIKKYRKELQVVAWDILLNIIERLLQQLQTLDSPELRTIVHDLLTTVEELCDQNEFHGSQERYFELVERCADQRPESSLLNLISYRAQSIHPAKDGWIQNLQALMERFFRSESRGAVRIKVLDVLSFVLLINRQFYEEELINSVVISQLSHIPEDKDHQVRKLATQLLVDLAEGCHTHHFNSLLDIIEKVMARSLSPPPELEERDVAAYSASLEDVKTAVLGLLVILQTKLYTLPASHATRVYEMLVSHIQLHYKHSYTLPIASSIRLQAFDFLLLLRADSLHRLGLPNKDGVVRFSPYCVCDYMEPERGSEKKTSGPLSPPTGPPGPAPAGPAVRLGSVPYSLLFRVLLQCLKQESDWKVLKLVLGRLPESLRYKVLIFTSPCSVDQLCSALCSMLSGPKTLERLRGAPEGFSRTDLHLAVVPVLTALISYHNYLDKTKQREMVYCLEQGLIHRCASQCVVALSICSVEMPDIIIKALPVLVVKLTHISATASMAVPLLEFLSTLARLPHLYRNFAAEQYASVFAISLPYTNPSKFNQYIVCLAHHVIAMWFIRCRLPFRKDFVPFITKGLRSNVLLSFDDTPEKDSFRARSTSLNERPKSLRIARPPKQGLNNSPPVKEFKESSAAEAFRCRSISVSEHVVRSRIQTSLTSASLGSADENSVAQADDSLKNLHLELTETCLDMMARYVFSNFTAVPKRSPVGEFLLAGGRTKTWLVGNKLVTVTTSVGTGTRSLLGLDSGELQSGPESSSSPGVHVRQTKEAPAKLESQAGQQVSRGARDRVRSMSGGHGLRVGALDVPASQFLGSATSPGPRTAPAAKPEKASAGTRVPVQEKTNLAAYVPLLTQGWAEILVRRPTGNTSWLMSLENPLSPFSSDINNMPLQELSNALMAAERFKEHRDTALYKSLSVPAASTAKPPPLPRSNTVASFSSLYQSSCQGQLHRSVSWADSAVVMEEGSPGEVPVLVEPPGLEDVEAALGMDRRTDAYSRSSSVSSQEEKSLHAEELVGRGIPIERVVSSEGGRPSVDLSFQPSQPLSKSSSSPELQTLQDILGDPGDKADVGRLSPEVKARSQSGTLDGESAAWSASGEDSRGQPEGPLPSSSPRSPSGLRPRGYTISDSAPSRRGKRVERDALKSRATASNAEKVPGINPSFVFLQLYHSPFFGDESNKPILLPNESQSFERSVQLLDQIPSYDTHKIAVLYVGEGQSNSELAILSNEHGSYRYTEFLTGLGRLIELKDCQPDKVYLGGLDVCGEDGQFTYCWHDDIMQAVFHIATLMPTKDVDKHRCDKKRHLGNDFVSIVYNDSGEDFKLGTIKGQFNFVHVIVTPLDYECNLVSLQCRKDMEGLVDTSVAKIVSDRNLPFVARQMALHANMASQVHHSRSNPTDIYPSKWIARLRHIKRLRQRICEEAAYSNPSLPLVHPPSHSKAPAQTPAEPTPGYEVGQRKRLISSVEDFTEFV  
s1:
MDYKDDDDKAKPTSKDSGLKEKFKILLGLGTPRPNPRSAEGKQTEFIITAEILRELSMECGLNNRIRMIGQICEVAKTKKFEEHAVEALWKAVADLLQPERPLEARHAVLALLKAIVQGQGERLGVLRALFFKVIKDYPSNEDLHERLEVFKALTDNGRHITYLEEELADFVLQWMDVGLSSEFLLVLVNLVKFNSCYLDEYIARMVQMICLLCVRTASSVDIEVSLQVLDAVVCYNCLPAESLPLFIVTLCRTINVKELCEPCWKLMRNLLGTHLGHSAIYNMCHLMEDRAYMEDAPLLRGAVFFVGMALWGAHRLYSLRNSPTSVLPSFYQAMACPNEVVSYEIVLSITRLIKKYRKELQVVAWDILLNIIERLLQQLQTLDSPELRTIVHDLLTTVEELCDQNEFHGSQERYFELVERCADQRPESSLLNLISYRAQSIHPAKDGWIQNLQALMERFFRSESRGAVRIKVLDVLSFVLLINRQFYEEELINSVVISQLSHIPEDKDHQVRKLATQLLVDLAEGCHTHHFNSLLDIIEKVMARSLSPPPELEERDVAAYSASLEDVKTAVLGLLVILQTKLYTLPASHATRVYEMLVSHIQLHYKHSYTLPIASSIRLQAFDFLLLLRADSLHRLGLPNKDGVVRFSPYCVCDYMEPERGSEKKTSGPLSPPTGPPGPAPAGPAVRLGSVPYSLLFRVLLQCLKQESDWKVLKLVLGRLPESLRYKVLIFTSPCSVDQLCSALCSMLSGPKTLERLRGAPEGFSRTDLHLAVVPVLTALISYHNYLDKTKQREMVYCLEQGLIHRCASQCVVALSICSVEMPDIIIKALPVLVVKLTHISATASMAVPLLEFLSTLARLPHLYRNFAAEQYASVFAISLPYTNPSKFNQYIVCLAHHVIAMWFIRCRLPFRKDFVPFITKGLRSNVLLSFDDTPEKDSFRARSTSLNERPKSLRIARPPKQGLNNSPPVKEFKESSAAEAFRCRSISVSEHVVRSRIQTSLTSASLGSADENSVAQADDSLKNLHLELTETCLDMMARYVFSNFTAVPKRSPVGEFLLAGGRTKTWLVGNKLVTVTTSVGTGTRSLLGLDSGELQSGPESSSSPGVHVRQTKEAPAKLESQAGQQVSRGARDRVRSMSGGHGLRVGALDVPASQFLGSATSPGPRTAPAAKPEKASAGTRVPVQEKTNLAAYVPLLTQGWAEILVRRPTGNTSWLMSLENPLSPFSSDINNMPLQELSNALMAAERFKEHRDTALYKSLSVPAASTAKPPPLPRSNT.......................DSAVVMEEGSPGEVPVLVEPPGLEDVEAALGMDRRTDAYSRSSSVSSQEEKSLHAEELVGRGIPIERVVSSEGGRPSVDLSFQPSQPLSKSSSSPELQTLQDILGDPGDKADVGRLSPEVKARSQSGTLDGESAAWSASGEDSRGQPEGPLPSSSPRSPSGLRPRGYTISDSAPSRRGKRVERDALKSRATASNAEKVPGINPSFVFLQLYHSPFFGDESNKPILLPNESQSFERSVQLLDQIPSYDTHKIAVLYVGEGQSNSELAILSNEHGSYRYTEFLTGLGRLIELKDCQPDKVYLGGLDVCGEDGQFTYCWHDDIMQAVFHIATLMPTKDVDKHRCDKKRHLGNDFVSIVYNDSGEDFKLGTIKGQFNFVHVIVTPLDYECNLVSLQCRKDMEGLVDTSVAKIVSDRNLPFVARQMALHANMASQVHHSRSNPTDIYPSKWIARLRHIKRLRQRICEEAAYSNPSLPLVHPPSHSKAPAQTPAEPTPGYEVGQRKRLISSVEDFTEFV  
s2:
........MAKPTSKDSGLKEKFKILLGLGTPRPNPRSAEGKQTEFIITAEILRELSMECGLNNRIRMIGQICEVAKTKKFEEHAVEALWKAVADLLQPERPLEARHAVLALLKAIVQGQGERLGVLRALFFKVIKDYPSNEDLHERLEVFKALTDNGRHITYLEEELADFVLQWMDVGLSSEFLLVLVNLVKFNSCYLDEYIARMVQMICLLCVRTASSVDIEVSLQVLDAVVCYNCLPAESLPLFIVTLCRTINVKELCEPCWKLMRNLLGTHLGHSAIYNMCHLMEDRAYMEDAPLLRGAVFFVGMALWGAHRLYSLRNSPTSVLPSFYQAMACPNEVVSYEIVLSITRLIKKYRKELQVVAWDILLNIIERLLQQLQTLDSPELRTIVHDLLTTVEELCDQNEFHGSQERYFELVERCADQRPESSLLNLISYRAQSIHPAKDGWIQNLQALMERFFRSESRGAVRIKVLDVLSFVLLINRQFYEEELINSVVISQLSHIPEDKDHQVRKLATQLLVDLAEGCHTHHFNSLLDIIEKVMARSLSPPPELEERDVAAYSASLEDVKTAVLGLLVILQTKLYTLPASHATRVYEMLVSHIQLHYKHSYTLPIASSIRLQAFDFLLLLRADSLHRLGLPNKDGVVRFSPYCVCDYMEPERGSEKKTSGPLSPPTGPPGPAPAGPAVRLGSVPYSLLFRVLLQCLKQESDWKVLKLVLGRLPESLRYKVLIFTSPCSVDQLCSALCSMLSGPKTLERLRGAPEGFSRTDLHLAVVPVLTALISYHNYLDKTKQREMVYCLEQGLIHRCASQCVVALSICSVEMPDIIIKALPVLVVKLTHISATASMAVPLLEFLSTLARLPHLYRNFAAEQYASVFAISLPYTNPSKFNQYIVCLAHHVIAMWFIRCRLPFRKDFVPFITKGLRSNVLLSFDDTPEKDSFRARSTSLNERPKSLRIARPPKQGLNNSPPVKEFKESSAAEAFRCRSISVSEHVVRSRIQTSLTSASLGSADENSVAQADDSLKNLHLELTETCLDMMARYVFSNFTAVPKRSPVGEFLLAGGRTKTWLVGNKLVTVTTSVGTGTRSLLGLDSGELQSGPESSSSPGVHVRQTKEAPAKLESQAGQQVSRGARDRVRSMSGGHGLRVGALDVPASQFLGSATSPGPRTAPAAKPEKASAGTRVPVQEKTNLAAYVPLLTQGWAEILVRRPTGNTSWLMSLENPLSPFSSDINNMPLQELSNALMAAERFKEHRDTALYKSLSVPAASTAKPPPLPRSNTVASFSSLYQSSCQGQLHRSVSWADSAVVMEEGSPGEVPVLVEPPGLEDVEAALGMDRRTDAYSRSSSVSSQEEKSLHAEELVGRGIPIERVVSSEGGRPSVDLSFQPSQPLSKSSSSPELQTLQDILGDPGDKADVGRLSPEVKARSQSGTLDGESAAWSASGEDSRGQPEGPLPSSSPRSPSGLRPRGYTISDSAPSRRGKRVERDALKSRATASNAEKVPGINPSFVFLQLYHSPFFGDESNKPILLPNESQSFERSVQLLDQIPSYDTHKIAVLYVGEGQSNSELAILSNEHGSYRYTEFLTGLGRLIELKDCQPDKVYLGGLDVCGEDGQFTYCWHDDIMQAVFHIATLMPTKDVDKHRCDKKRHLGNDFVSIVYNDSGEDFKLGTIKGQFNFVHVIVTPLDYECNLVSLQCRKDMEGLVDTSVAKIVSDRNLPFVARQMALHANMASQVHHSRSNPTDIYPSKWIARLRHIKRLRQRICEEAAYSNPSLPLVHPPSHSKAPAQTPAEPTPGYEVGQRKRLISSVEDFTEFV  
s1:
.................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................MAQQANVGELLAMLDSPMLGVRDDVTAVFKENLNSDRGPMLVNTLVDYYLETSSQPALHILTTLQEPHDKHLLDRINEYVGKAATRLSILSLLGHVIRLQPSWKHKLSQAPLLPSLLKCLKMDTDVVVLTTGVLVLITMLPMIPQSGKQHLLDFFDIFGRLSSWCLKKPGHVAEVYLVHLHASVYALFHRLYGMYPCNFVSFLRSHYSMKENLETFEEVVKPMMEHVRIHPELVTGSKDHELDPRRWKRLETHDVVIECAKISLDPTEASYEDGYSVSHQISARFPHRSADVTTSPYADTQNSYGCATSTPYSTSRLMLLNMPGQLPQTLSSPSTRLITEPPQATLWSPSMVCGMTTPPTSPGNVP.PDLSHPYS.....KVFGTTAGGKGTPLGTPATSPPPAPLCHSDDYVHISLPQATVTPPRKEERMDSARPCLHRQHHLLNDRGSEEPPGSKGSV.TLSDLPGFLGDLASEEDSIEKDKEEAAISRELS....EITTAEAEPVVPRGGFDSPFYR.DSLPGSQRKTHSAASSSQ...GASVNPEPLHSSLDKLGPDTPKQAFTPIDLPCGSADESPAGDREC...QTSLETSIFTPSPCKIPPPTRVGFGSGQPPPYDHLFEVALPKTAHHFVIRKTEELLKKAKGNTEEDGVPSTSPMEVLDRLIQQGADAHSKELNK...LPLPSKSVD............WTHFGGSPPSDEIRTLRDQLLLLHNQLLYERFKRQQHALRNRRLLRKVIKAAALEEHNAAMKDQLKLQEKDIQMWKVSLQKEQARYNQLQEQRDTMVTKLHSQIRQLQHDREEFYNQSQELQTKLEDCRNMIAELRIELKKANNKVCHTELLLSQVSQKLSNSESVQQQMEFLNRQLLVLGEVNELYLEQLQNKHSDTTKEVEMMKAAYRKELEKNRSHVLQQTQRLDTSQKRILELESHLAKKDHLLLEQKKYLEDVKLQARGQLQAAESRYEAQKRITQVFELEILDLYGRLEKDGLLKKLEEEKAEAAEAAEERLDCCNDGCSDSMVGHNEEASGHNGETKTPRPSSARGSSGSRGGGGSSSSSSELSTPEKPPHQRAGPFSSRWETTMGEASASIPTTVGSLPSSKSFLGMKARELFRNKSESQCDEDGMTSSLSESLKTELGKDLGVEAKIPLNLDGPHPSPPTPDSVGQLHIMDYNETHHEHSGTKLGPEQKLISEEDLNSAVDHHHHHH  
s2:
MAKPTSKDSGLKEKFKILLGLGTPRPNPRSAEGKQTEFIITAEILRELSMECGLNNRIRMIGQICEVAKTKKFEEHAVEALWKAVADLLQPERPLEARHAVLALLKAIVQGQGERLGVLRALFFKVIKDYPSNEDLHERLEVFKALTDNGRHITYLEEELADFVLQWMDVGLSSEFLLVLVNLVKFNSCYLDEYIARMVQMICLLCVRTASSVDIEVSLQVLDAVVCYNCLPAESLPLFIVTLCRTINVKELCEPCWKLMRNLLGTHLGHSAIYNMCHLMEDRAYMEDAPLLRGAVFFVGMALWGAHRLYSLRNSPTSVLPSFYQAMACPNEVVSYEIVLSITRLIKKYRKELQVVAWDILLNIIERLLQQLQTLDSPELRTIVHDLLTTVEELCDQNEFHGSQERYFELVERCADQRPESSLLNLISYRAQSIHPAKDGWIQNLQALMERFFRSESRGAVRIKVLDVLSFVLLINRQFYEEELINSVVISQLSHIPEDKDHQVRKLATQLLVDLAEGCHTHHFNSLLDIIEKVMARSLSPPPELEERDVAAYSASLEDVKTAVLGLLVILQTKLYTLPASHATRVYEMLVSHIQLHYKHSYTLPIASSIRLQAFDFLLLLRADSLHRLGLPNKDGVVRFSPYCVCDYMEPERGSEKKTSGPLSPPTGPPGPAPAGPAVRLGSVPYSLLFRVLLQCLKQESDWKVLKLVLGRLPESLRYKVLIFTSPCSVDQLCSALCSMLSGPKTLERLRGAPEGFSRTDLHLAVVPVLTALISYHNYLDKTKQREMVYCLEQGLIHRCASQCVVALSICSVEMPDIIIKALPVLVVKLTHISATASMAVPLLEFLSTLARLPHLYRNFAAEQYASVFAISLPYTNPSKFNQYIVCLAHHVIAMWFIRCRLPFRKDFVPFITKGLRSNV..LLSFDDTP....EKDSFRARSTSLNERPKSLRIARPPKQGLN.NSPPVKEFKESSAAEAFRCRSISVSEHVVRSRIQTSLTSA.....SLGSADENSVAQADDSLKNLHLELTETCLDMMARYVFSNFTAVPK.....RSPVGEFLLAGGRTKTWLVGNK.......LVTVTTSVGTGTRSLLGLDSGELQSGPESSSSPGVHVRQTKEA..PAKLESQAGQQVSRGARD.....RVRSMSGGHGLRVG....ALD.VPASQFLG.......SATSP....GPRTAPAAKPEKA.SAGTRVPVQEK....TNLAAYVPLLTQGWAEILVRRPTGNTSWLMSLENPLSPFSSDINNMPLQELSNALMAAERFKEHRDTALYKSLSVPAASTAKPP............PLPRSNTVASFSSLYQSSCQGQLHRSVSWA.DSAVVMEEGSPGEVPVLVEPPG....LEDVEAALGMDRRTDAYSRSSSVSSQEEKSLHAEELVGRG...IPIERVVSSEGGRPSVDLSFQPSQPLSKSSSSPE.LQTLQDILGDPGDKADVGRLSPEVKARSQSGTLDGESAAWSASGEDSRGQPEG...PLPSSSPRSPSGLRPRGYTISDSAPSRRGKRVER...DALKSRATASNAEKVPGINPSFVFLQLYH..SPFFGDESNKPILLPNESQSFERSVQLLDQIPSYDTHKIAVLYVGEGQS.NSELAILSNE..HGSYRYTEFLTGLGRLIE..LKDCQPDKVYLGGLDVCGEDGQFTYCWHDDIMQAVFHIATLMPTKDVDKHRCDKKRHLGNDFVSIVYNDSGE.DFKLGTIKGQFNFVHVIVTPLDYE.CNLVSLQCRKDMEGLVDTSVAKIVS..DRNLPFVARQMALHANMASQVHHSRSNPTDI....YPSKWIARLRHIKRLRQRICEEAAYSNPSLPLVHPPSHSKAPAQTPAEPTPGYEVGQRKRLISSVEDFTEFV............................................................................................................................................................................................................................................  
s1:
.................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................MAQQANVGELLAMLDSPMLGVRDDVTAVFKENLNSDRGPMLVNTLVDYYLETSSQPALHILTTLQEPHDKHLLDRINEYVGKAATRLSILSLLGHVIRLQPSWKHKLSQAPLLPSLLKCLKMDTDVVVLTTGVLVLITMLPMIPQSGKQHLLDFFDIFGRLSSWCLKKPGHVAEVYLVHLHASVYALFHRLYGMYPCNFVSFLRSHYSMKENLETFEEVVKPMMEHVRIHPELVTGSKDHELDPRRWKRLETHDVVIECAKISLDPTEASYEDGYSVSHQISARFPHRSADVTTSPYADTQNSYGCATSTPYSTSRLMLLNMPGQLPQTLSSPSTRLITEPPQATLWSPSMVCGMTTPPTSPGNVP.PDLSHPYS.....KVFGTTAGGKGTPLGTPATSPPPAPLCHSDDYVHISLPQATVTPPRKEERMDSARPCLHRQHHLLNDRGSEEPPGSKGSV.TLSDLPGFLGDLASEEDSIEKDKEEAAISRELS....EITTAEAEPVVPRGGFDSPFYR.DSLPGSQRKTHSAASSSQ...GASVNPEPLHSSLDKLGPDTPKQAFTPIDLPCGSADESPAGDREC...QTSLETSIFTPSPCKIPPPTRVGFGSGQPPPYDHLFEVALPKTAHHFVIRKTEELLKKAKGNTEEDGVPSTSPMEVLDRLIQQGADAHSKELNK.LPLPSKSVDW...THFGGSPPSDEI..........RTLRDQLLLLHNQLLYERFKRQQHALRNRRLLRKVIKAAALEEHNAAMKDQLKLQEKDIQMWKVSLQKEQARYNQLQEQRDTMVTKLHSQIRQLQHDREEFYNQSQELQTKLEDCRNMIAELRIELKKANNKVCHTELLLSQVSQKLSNSESVQQQMEFLNRQLLVLGEVNELYLEQLQNKH...SDTTKEVEMMKAAYRKELEKNRSHVLQQTQRLDTSQKRILELESHLAKKDHLLLEQKKYLEDVKLQARGQLQAAESRYEAQKRITQVFELEILDLYGRLEKDGLLKKLEEEKAEAAEAAEERLDCCNDGCSDSMVGHNEEASGHNGETKTPRPSSARGSSGSRGGGGSSSSSSELSTPEKPPHQRAGPFSSRWETTMGEASASIPTTVGSLPSSKSFLGMKARELFRNKSESQCDEDGMTSSLSESLKTELGKDLGVEAKIPLNLDGPHPSPPTPDSVGQLHIMDYNETHHEHSGTKLGPEQKLISEEDLNSAVDHHHHHH  
s2:
MAKPTSKDSGLKEKFKILLGLGTPRPNPRSAEGKQTEFIITAEILRELSMECGLNNRIRMIGQICEVAKTKKFEEHAVEALWKAVADLLQPERPLEARHAVLALLKAIVQGQGERLGVLRALFFKVIKDYPSNEDLHERLEVFKALTDNGRHITYLEEELADFVLQWMDVGLSSEFLLVLVNLVKFNSCYLDEYIARMVQMICLLCVRTASSVDIEVSLQVLDAVVCYNCLPAESLPLFIVTLCRTINVKELCEPCWKLMRNLLGTHLGHSAIYNMCHLMEDRAYMEDAPLLRGAVFFVGMALWGAHRLYSLRNSPTSVLPSFYQAMACPNEVVSYEIVLSITRLIKKYRKELQVVAWDILLNIIERLLQQLQTLDSPELRTIVHDLLTTVEELCDQNEFHGSQERYFELVERCADQRPESSLLNLISYRAQSIHPAKDGWIQNLQALMERFFRSESRGAVRIKVLDVLSFVLLINRQFYEEELINSVVISQLSHIPEDKDHQVRKLATQLLVDLAEGCHTHHFNSLLDIIEKVMARSLSPPPELEERDVAAYSASLEDVKTAVLGLLVILQTKLYTLPASHATRVYEMLVSHIQLHYKHSYTLPIASSIRLQAFDFLLLLRADSLHRLGLPNKDGVVRFSPYCVCDYMEPERGSEKKTSGPLSPPTGPPGPAPAGPAVRLGSVPYSLLFRVLLQCLKQESDWKVLKLVLGRLPESLRYKVLIFTSPCSVDQLCSALCSMLSGPKTLERLRGAPEGFSRTDLHLAVVPVLTALISYHNYLDKTKQREMVYCLEQGLIHRCASQCVVALSICSVEMPDIIIKALPVLVVKLTHISATASMAVPLLEFLSTLARLPHLYRNFAAEQYASVFAISLPYTNPSKFNQYIVCLAHHVIAMWFIRCRLPFRKDFVPFITKGLRSNV..LLSFDDTP....EKDSFRARSTSLNERPKSLRIARPPKQGLN.NSPPVKEFKESSAAEAFRCRSISVSEHVVRSRIQTSLTSA.....SLGSADENSVAQADDSLKNLHLELTETCLDMMARYVFSNFTAVPK.....RSPVGEFLLAGGRTKTWLVGNK.......LVTVTTSVGTGTRSLLGLDSGELQSGPESSSSPGVHVRQTKEA..PAKLESQAGQQVSRGARDRVRSMSGGHGLRVGALDVPASQFLGSAT.....................SPGPRTAPAAKPEKA.SAGTRVPVQEK....TNLAAYVPLLTQGWAEILVRRPTGNTSWLMSLENPLSPFSSDINNMPLQELSNALMAAERFKEHRDTALYKSLSVPAASTAKPP............PLPRSNTVASFSSLYQSSCQGQLHRSVSWA.DSAVVMEEGSPGEVPVLVEPPG....LEDVEAALGMDRRTDAYSRSSSVSSQEEKSLHAEELVGRG...IPIERVVSSEGGRPSVDLSFQPSQPLSKSSSSPE.LQTLQDILGDPGDKADVGRLSPEVKARSQSGTLDGESAAWSASGEDSRGQPEG...PLPSSSPRSPSGLRPRGYTISDSAPSRRGKRVER...DALKSRATASNAEKVPGINPSFVFLQLYH..SPFFGDESNKPILLPNESQSFERSVQLLDQIPSYDTHKIAVLYVGEGQSNSELAILSNE..HGSYRYTEFLTGLGRLIE..LKDCQPDKVYLGGLDVCGEDGQFTYCWHDDIMQAVFHIATLMPTKDVDKHRCDKKRHLGNDFVSIVYNDSGE.DFKLGTIKGQFNFVHVIVTPLDYE.CNLVSLQCRKDMEGLVDTSVAKIVS..DRNLPFVARQMALHANMASQVHHSRSNPTDIYPSKWIARLRHIKRLRQRICEEAAYSNPSLP.LVHPPSHSKAPAQTPAEPTPGYEVG..QRKRLISSVEDFTEFV................................................................................................................................................................................................................................................  
s1:
...........................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................MTEDSQRNFRSVYYEKVGF....RGVEEKKSLEILLKDDRLDTEKLCTFSQRFPLPSMYRALVWKVLLGILPPHHESHAKVMMYRKEQYLDVLHALKVVRFVSDATPQAEVYLRMYQLES.GKLPRSPSFPLEPDDEVFLAIAKAMEEMVEDSVDCYWITRRFVNQLNTKYRDSLPQLPKAFEQYLNLEDGRLLTHLRMCSAAPKLPYDLWFKRCFAGCLPESSLQRVWDKVVSGSCKILVFVAVEILLTFKIKVMALNSAEKITKFLENIPQDSSDAIVSKAIDLWHKHCGTPVHSSDYKDDDDK  
s2:
MAKPTSKDSGLKEKFKILLGLGTPRPNPRSAEGKQTEFIITAEILRELSMECGLNNRIRMIGQICEVAKTKKFEEHAVEALWKAVADLLQPERPLEARHAVLALLKAIVQGQGERLGVLRALFFKVIKDYPSNEDLHERLEVFKALTDNGRHITYLEEELADFVLQWMDVGLSSEFLLVLVNLVKFNSCYLDEYIARMVQMICLLCVRTASSVDIEVSLQVLDAVVCYNCLPAESLPLFIVTLCRTINVKELCEPCWKLMRNLLGTHLGHSAIYNMCHLMEDRAYMEDAPLLRGAVFFVGMALWGAHRLYSLRNSPTSVLPSFYQAMACPNEVVSYEIVLSITRLIKKYRKELQVVAWDILLNIIERLLQQLQTLDSPELRTIVHDLLTTVEELCDQNEFHGSQERYFELVERCADQRPESSLLNLISYRAQSIHPAKDGWIQNLQALMERFFRSESRGAVRIKVLDVLSFVLLINRQFYEEELINSVVISQLSHIPEDKDHQVRKLATQLLVDLAEGCHTHHFNSLLDIIEKVMARSLSPPPELEERDVAAYSASLEDVKTAVLGLLVILQTKLYTLPASHATRVYEMLVSHIQLHYKHSYTLPIASSIRLQAFDFLLLLRADSLHRLGLPNKDGVVRFSPYCVCDYMEPERGSEKKTSGPLSPPTGPPGPAPAGPAVRLGSVPYSLLFRVLLQCLKQESDWKVLKLVLGRLPESLRYKVLIFTSPCSVDQLCSALCSMLSGPKTLERLRGAPEGFSRTDLHLAVVPVLTALISYHNYLDKTKQREMVYCLEQGLIHRCASQCVVALSICSVEMPDIIIKALPVLVVKLTHISATASMAVPLLEFLSTLARLPHLYRNFAAEQYASVFAISLPYTNPSKFNQYIVCLAHHVIAMWFIRCRLPFRKDFVPFITKGLRSNVLLSFDDTPEKDSFRARSTSLNERPKSLRIARPPKQGLNNSPPVKEFKESSAAEAFRCRSISVSEHVVRSRIQTSLTSASLGSADENSVAQADDSLKNLHLELTETCLDMMARYVFSNFTAVPKRSPVGEFLLAGGRTKTWLVGNKLVTVTTSVGTGTRSLLGLDSGELQSGPESSSSPGVHVRQTKEAPAKLESQAGQQVSRGARDRVRSMSGGHGLRVGALDVPASQFLGSATSPGPRTAPAAKPEKASAGTRVPVQEKTNLAAYVPLLTQGWAEILVRRPTGNTSWLMSLENPLSPFSSDINNMPLQELSNALMAAERFKEHRDTALYKSLSVPAASTAKPPPLPRSNTVASFSSLYQSSCQGQLHRSVSWADSAVVMEEGSPGEVPVLVEPPGLEDVEAALGMDRRTDAYSRSSSVSSQEEKSLHAEELVGRGIPIERVVSSEGGRPSVDLSFQPSQPLSKSSSSPELQTLQDILGDPGDKADVGRLSPEVKARSQSGTLDGESAAWSASGEDSRGQPEGPLPSSSPRSPSGLRPRGYTISDSAPSRRGKRVERDALKSRATASNAEKVPGINPSFVFLQLYHSPFFGDESNKPILLPNESQSFERSVQLLDQIPSYDTHKIAVLYVGEGQSNSELAILSNEHGSYRYTEFLTGLGRLIELKDCQPDKVYLGGLDVCGEDGQFTYCWHDDIMQAVFHIATLMPTKDVDKHRCDKKRHLGNDFVSIVYNDSGEDFKLGTIKGQFNFVHVIVTPLDYECNLVSLQCRKDMEGL.....VDTSVAKIVSDR.NLPFVARQMALHANMASQVHHSRSNP.TDIYPSKWIARLRHIKRLRQRICEEAAYSNPSLPLVHPPSHSKAPAQT..PAEPTPGYEVGQRKRLISSVEDFTEFV.....................................................................................................................................................  
s1:
........................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................MHHHHHHGLLYAGFNQ.DHGCFACGMENGFRVYNT..DPLKEKEKQEFLEGGVGHVEMLFRCNYLALVGGGKKKVMIWDDLKKKTVIEIEFSTEVKAVKLRRDRIVVVLDSMIKVFTFTHNPHQLHVFETCYNPKGLCVLCPNSN....NSLLAFPGTHTGHVQLVDLASTEKPPVDIPAHEGVLSCIALNLQGT........RIATASEKGTLIRIFD.....TSSGHLIQELRRGSQAANIYCINFNQDASLICVSSDHGTVHIFAAEDPKSKWSFSKFQVPSGSPCICAFGTE.PNAVIAICADGSYYKFLFNPK....GECIRDVYAQFLEMTDDKL.....................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................  
s2:
MAKPTSKDSGLKEKFKILLGLGTPRPNPRSAEGKQTEFIITAEILRELSMECGLNNRIRMIGQICEVAKTKKFEEHAVEALWKAVADLLQPERPLEARHAVLALLKAIVQGQGERLGVLRALFFKVIKDYPSNEDLHERLEVFKALTDNGRHITYLEEELADFVLQWMDVGLSSEFLLVLVNLVKFNSCYLDEYIARMVQMICLLCVRTASSVDIEVSLQVLDAVVCYNCLPAESLPLFIVTLCRTINVKELCEPCWKLMRNLLGTHLGHSAIYNMCHLMEDRAYMEDAPLLRGAVFFVGMALWGAHRLYSLRNSPTSVLPSFYQAMACPNEVVSYEIVLSITRLIKKYRKELQVVAWDILLNIIERLLQQLQTLDSPELRTIVHDLLTTVEELCDQNEFHGSQERYFELVERCADQRPESSLLNLISYRAQSIHPAKDGWIQNLQALMERFFRSESRGAVRIKVLDVLSFVLLINRQFYEEELINSVVISQLSHIPEDKDHQVRKLATQLLVDLAEGCHTHHFNSLLDIIEKVMARSLSPPPELEERDVAAYSASLEDVKTAVLGLLVILQTKLYTLPASHATRVYEMLVSHIQLHYKHSYTLPIASSIRLQAFDFLLLLRADSLHRLGLPNKDGVVRFSPYCVCDYMEPERGSEKKTSGPLSPPTGPPGPAPAGPAVRLGSVPYSLLFRVLLQCLKQESDWKVLKLVLGRLPESLRYKVLIFTSPCSVDQLCSALCSMLSGPKTLERLRG.APEGFSRTDLHLAVVPVLTALISYHNYLDKTKQREMVYCLEQGLIH.....RCASQCVVALSICSVEMPDIIIKALPVLVVKLTHISATASMAVPLLEFLSTLARL......PHLYRNFAAEQYASVFAISLPYTNPSKFNQYIVCLAHHVIAMWFIRCRLPFRKDFVPFITKGLRSNVLLSFDDTPEKDSFRARSTSLNERPKSLRIARPPKQGLNNSPPVKEFKESSAAEAFRCRS.......ISVSEHVVRSRIQTSLTSASLGSADENSVAQADDSLKNLHLELTETCLDMMARYVFSNFTAVPKRSPVGEFLLAGGRTKTWLVGNKLVTVTTSVGTGTRSLLGLDSGELQSGPESSSSPGVHVRQTKEAPAKLESQAGQQVSRGARDRVRSMSGGHGLRVGALDVPASQFLGSATSPGPRTAPAAKPEKASAGTRVPVQEKTNLAAYVPLLTQGWAEILVRRPTGNTSWLMSLENPLSPFSSDINNMPLQELSNALMAAERFKEHRDTALYKSLSVPAASTAKPPPLPRSNTVASFSSLYQSSCQGQLHRSVSWADSAVVMEEGSPGEVPVLVEPPGLEDVEAALGMDRRTDAYSRSSSVSSQEEKSLHAEELVGRGIPIERVVSSEGGRPSVDLSFQPSQPLSKSSSSPELQTLQDILGDPGDKADVGRLSPEVKARSQSGTLDGESAAWSASGEDSRGQPEGPLPSSSPRSPSGLRPRGYTISDSAPSRRGKRVERDALKSRATASNAEKVPGINPSFVFLQLYHSPFFGDESNKPILLPNESQSFERSVQLLDQIPSYDTHKIAVLYVGEGQSNSELAILSNEHGSYRYTEFLTGLGRLIELKDCQPDKVYLGGLDVCGEDGQFTYCWHDDIMQAVFHIATLMPTKDVDKHRCDKKRHLGNDFVSIVYNDSGEDFKLGTIKGQFNFVHVIVTPLDYECNLVSLQCRKDMEGLVDTSVAKIVSDRNLPFVARQMALHANMASQVHHSRSNPTDIYPSKWIARLRHIKRLRQRICEEAAYSNPSLPLVHPPSHSKAPAQTPAEPTPGYEVGQRKRLISSVEDFTEFV  
s1:
...................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................????????????  
s2:
MAKPTSKDSGLKEKFKILLGLGTPRPNPRSAEGKQTEFIITAEILRELSMECGLNNRIRMIGQICEVAKTKKFEEHAVEALWKAVADLLQPERPLEARHAVLALLKAIVQGQGERLGVLRALFFKVIKDYPSNEDLHERLEVFKALTDNGRHITYLEEELADFVLQWMDVGLSSEFLLVLVNLVKFNSCYLDEYIARMVQMICLLCVRTASSVDIEVSLQVLDAVVCYNCLPAESLPLFIVTLCRTINVKELCEPCWKLMRNLLGTHLGHSAIYNMCHLMEDRAYMEDAPLLRGAVFFVGMALWGAHRLYSLRNSPTSVLPSFYQAMACPNEVVSYEIVLSITRLIKKYRKELQVVAWDILLNIIERLLQQLQTLDSPELRTIVHDLLTTVEELCDQNEFHGSQERYFELVERCADQRPESSLLNLISYRAQSIHPAKDGWIQNLQALMERFFRSESRGAVRIKVLDVLSFVLLINRQFYEEELINSVVISQLSHIPEDKDHQVRKLATQLLVDLAEGCHTHHFNSLLDIIEKVMARSLSPPPELEERDVAAYSASLEDVKTAVLGLLVILQTKLYTLPASHATRVYEMLVSHIQLHYKHSYTLPIASSIRLQAFDFLLLLRADSLHRLGLPNKDGVVRFSPYCVCDYMEPERGSEKKTSGPLSPPTGPPGPAPAGPAVRLGSVPYSLLFRVLLQCLKQESDWKVLKLVLGRLPESLRYKVLIFTSPCSVDQLCSALCSMLSGPKTLERLRGAPEGFSRTDLHLAVVPVLTALISYHNYLDKTKQREMVYCLEQGLIHRCASQCVVALSICSVEMPDIIIKALPVLVVKLTHISATASMAVPLLEFLSTLARLPHLYRNFAAEQYASVFAISLPYTNPSKFNQYIVCLAHHVIAMWFIRCRLPFRKDFVPFITKGLRSNVLLSFDDTPEKDSFRARSTSLNERPKSLRIARPPKQGLNNSPPVKEFKESSAAEAFRCRSISVSEHVVRSRIQTSLTSASLGSADENSVAQADDSLKNLHLELTETCLDMMARYVFSNFTAVPKRSPVGEFLLAGGRTKTWLVGNKLVTVTTSVGTGTRSLLGLDSGELQSGPESSSSPGVHVRQTKEAPAKLESQAGQQVSRGARDRVRSMSGGHGLRVGALDVPASQFLGSATSPGPRTAPAAKPEKASAGTRVPVQEKTNLAAYVPLLTQGWAEILVRRPTGNTSWLMSLENPLSPFSSDINNMPLQELSNALMAAERFKEHRDTALYKSLSVPAASTAKPPPLPRSNTVASFSSLYQSSCQGQLHRSVSWADSAVVMEEGSPGEVPVLVEPPGLEDVEAALGMDRRTDAYSRSSSVSSQEEKSLHAEELVGRGIPIERVVSSEGGRPSVDLSFQPSQPLSKSSSSPELQTLQDILGDPGDKADVGRLSPEVKARSQSGTLDGESAAWSASGEDSRGQPEGPLPSSSPRSPSGLRPRGYTISDSAPSRRGKRVERDALKSRATASNAEKVPGINPSFVFLQLYHSPFFGDESNKPILLPNESQSFERSVQLLDQIPSYDTHKIAVLYVGEGQSNSELAILSNEHGSYRYTEFLTGLGRLIELKDCQPDKVYLGGLDVCGEDGQFTYCWHDDIMQAVFHIATLMPTKDVDKHRCDKKRHLGNDFVSIVYNDSGEDFKLGTIKGQFNFVHVIVTPLDYECNLVSLQCRKDMEGLVDTSVAKIVSDRNLPFVARQMALHANMASQVHHSRSNPTDIYPSKWIARLRHIKRLRQRICEEAAYSNPSLPLVHPPSHSKAPAQTPAEPTPGYEVGQRKRLISSVEDFTEFV  
s1:
...................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................????????????  
s2:
MAKPTSKDSGLKEKFKILLGLGTPRPNPRSAEGKQTEFIITAEILRELSMECGLNNRIRMIGQICEVAKTKKFEEHAVEALWKAVADLLQPERPLEARHAVLALLKAIVQGQGERLGVLRALFFKVIKDYPSNEDLHERLEVFKALTDNGRHITYLEEELADFVLQWMDVGLSSEFLLVLVNLVKFNSCYLDEYIARMVQMICLLCVRTASSVDIEVSLQVLDAVVCYNCLPAESLPLFIVTLCRTINVKELCEPCWKLMRNLLGTHLGHSAIYNMCHLMEDRAYMEDAPLLRGAVFFVGMALWGAHRLYSLRNSPTSVLPSFYQAMACPNEVVSYEIVLSITRLIKKYRKELQVVAWDILLNIIERLLQQLQTLDSPELRTIVHDLLTTVEELCDQNEFHGSQERYFELVERCADQRPESSLLNLISYRAQSIHPAKDGWIQNLQALMERFFRSESRGAVRIKVLDVLSFVLLINRQFYEEELINSVVISQLSHIPEDKDHQVRKLATQLLVDLAEGCHTHHFNSLLDIIEKVMARSLSPPPELEERDVAAYSASLEDVKTAVLGLLVILQTKLYTLPASHATRVYEMLVSHIQLHYKHSYTLPIASSIRLQAFDFLLLLRADSLHRLGLPNKDGVVRFSPYCVCDYMEPERGSEKKTSGPLSPPTGPPGPAPAGPAVRLGSVPYSLLFRVLLQCLKQESDWKVLKLVLGRLPESLRYKVLIFTSPCSVDQLCSALCSMLSGPKTLERLRGAPEGFSRTDLHLAVVPVLTALISYHNYLDKTKQREMVYCLEQGLIHRCASQCVVALSICSVEMPDIIIKALPVLVVKLTHISATASMAVPLLEFLSTLARLPHLYRNFAAEQYASVFAISLPYTNPSKFNQYIVCLAHHVIAMWFIRCRLPFRKDFVPFITKGLRSNVLLSFDDTPEKDSFRARSTSLNERPKSLRIARPPKQGLNNSPPVKEFKESSAAEAFRCRSISVSEHVVRSRIQTSLTSASLGSADENSVAQADDSLKNLHLELTETCLDMMARYVFSNFTAVPKRSPVGEFLLAGGRTKTWLVGNKLVTVTTSVGTGTRSLLGLDSGELQSGPESSSSPGVHVRQTKEAPAKLESQAGQQVSRGARDRVRSMSGGHGLRVGALDVPASQFLGSATSPGPRTAPAAKPEKASAGTRVPVQEKTNLAAYVPLLTQGWAEILVRRPTGNTSWLMSLENPLSPFSSDINNMPLQELSNALMAAERFKEHRDTALYKSLSVPAASTAKPPPLPRSNTVASFSSLYQSSCQGQLHRSVSWADSAVVMEEGSPGEVPVLVEPPGLEDVEAALGMDRRTDAYSRSSSVSSQEEKSLHAEELVGRGIPIERVVSSEGGRPSVDLSFQPSQPLSKSSSSPELQTLQDILGDPGDKADVGRLSPEVKARSQSGTLDGESAAWSASGEDSRGQPEGPLPSSSPRSPSGLRPRGYTISDSAPSRRGKRVERDALKSRATASNAEKVPGINPSFVFLQLYHSPFFGDESNKPILLPNESQSFERSVQLLDQIPSYDTHKIAVLYVGEGQSNSELAILSNEHGSYRYTEFLTGLGRLIELKDCQPDKVYLGGLDVCGEDGQFTYCWHDDIMQAVFHIATLMPTKDVDKHRCDKKRHLGNDFVSIVYNDSGEDFKLGTIKGQFNFVHVIVTPLDYECNLVSLQCRKDMEGLVDTSVAKIVSDRNLPFVARQMALHANMASQVHHSRSNPTDIYPSKWIARLRHIKRLRQRICEEAAYSNPSLPLVHPPSHSKAPAQTPAEPTPGYEVGQRKRLISSVEDFTEFV  

> isolde restrain distances "#1.2/A" templateAtoms "#2.1/A" perChain false
> adjustForConfidence true useCoordinateAlignment false kappa 4.40 fallOff
> 2.50 groupName "Reference Distance Restraints"

ISOLDE: Checking and correcting nomenclature for (pseudo)symmetric side
chains...  
[Repeated 1 time(s)]ISOLDE: Corrected atom nomenclature of 279 residues in
model #2.1 to IUPAC-IUB standards.  
Computing secondary structure  
[Repeated 1 time(s)]

> isolde restrain torsions #1.2/A templateResidues #2.1/A adjustForConfidence
> true sidechains true springConstant 250.00 alpha 0.20

ISOLDE: Checking and correcting nomenclature for (pseudo)symmetric side
chains...  
[Repeated 1 time(s)]Computing secondary structure  
[Repeated 1 time(s)]

> matchmaker #2.3 to #1.2

Computing secondary structure  
[Repeated 1 time(s)]  Parameters  
---  
Chain pairing | bb  
Alignment algorithm | Needleman-Wunsch  
Similarity matrix | BLOSUM-62  
SS fraction | 0.3  
Gap open (HH/SS/other) | 18/18/6  
Gap extend | 1  
SS matrix |  |  | H | S | O  
---|---|---|---  
H | 6 | -9 | -6  
S |  | 6 | -6  
O |  |  | 4  
Iteration cutoff | 2  
  
Matchmaker 9ce3, chain C (#1.2) with AlphaFold TSC1_HUMAN chain C, chain C
(#2.3), sequence alignment score = 5135.8  
RMSD between 262 pruned atom pairs is 0.693 angstroms; (across all 616 pairs:
88.426)  
  

> color #2.3 bychain

> color #2.3 byhetero

> color modify #2.3 hue + 50

ISOLDE: attempting to load PAE matrix for model #2.3 from the AlphaFold-EBI
database. If this fails or you wish to use a different PAE matrix, use the
"Load PAE matrix" button in ISOLDE's reference model restraints widget.  

> alphafold pae #2.3 uniprotId Q92574 plot false

Fetching compressed AlphaFold PAE Q92574 from
https://alphafold.ebi.ac.uk/files/AF-Q92574-F1-predicted_aligned_error_v4.json  
Computing secondary structure  
[Repeated 1 time(s)]s1:
MDYKDDDDKAKPTSKDSGLKEKFKILLGLGTPRPNPRSAEGKQTEFIITAEILRELSMECGLNNRIRMIGQICEVAKTKKFEEHAVEALWKAVADLLQPERPLEARHAVLALLKAIVQGQGERLGVLRALFFKVIKDYPSNEDLHERLEVFKALTDNGRHITYLEEELADFVLQWMDVGLSSEFLLVLVNLVKFNSCYLDEYIARMVQMICLLCVRTASSVDIEVSLQVLDAVVCYNCLPAESLPLFIVTLCRTINVKELCEPCWKLMRNLLGTHLGHSAIYNMCHLMEDRAYMEDAPLLRGAVFFVGMALWGAHRLYSLRNSPTSVLPSFYQAMACPNEVVSYEIVLSITRLIKKYRKELQVVAWDILLNIIERLLQQLQTLDSPELRTIVHDLLTTVEELCDQNEFHGSQERYFELVERCADQRPESSLLNLISYRAQSIHPAKDGWIQNLQALMERFFRSESRGAVRIKVLDVLSFVLLINRQFYEEELINSVVISQLSHIPEDKDHQVRKLATQLLVDLAEG...CHTHHFNSLLDIIEKVMARSLSPPPELEERDVAAYSASLEDVKTAVLGLLVILQTKLYTL......PASHATRVYEMLVSHIQLHYKH.....SYTLPIASSIRLQAFDFLLLLRADSLHRLGLPNKDGVVRFSPYCVCDYMEPERGSEKKTSGPLSPPTGPPGPAPAGPAVRLGSVPYSLLFRVLLQCLKQESDWKVLKLVLGRLPESLR..YKVLIFTSPCSVDQLCSALCSMLSGPKTLERLRGAPEGFSRTDLHLAVVPVLTALISYHNYLDKTKQREMVYCLEQGLIHRCASQCVVALSICSVEMPDIIIKALPVLVVKLTHISATASMAVPLLEFLSTLARLPHLYRNFAAEQYASVFAISLPYTNPSKFNQYIVCLAHHVIAMWFIRCRLPFRKDFVPFITKGLRSNVLLSFDDTPEKDSFRARSTSLNERPKSLRIARPPKQGLNNSPPVKEFKESSAAEAFRCRSISVSEHVVRSRIQTSLTSASLGSADENSVAQADDSLKNLHLELTETCLDMMARYVFSNFTAVPKRSPVGEFLLAG.GRTKTWLVGNKLVTVTTSVGTGTRSLLGLDSGELQSGPESSSSPGVHVRQTKEAPAKLESQAGQQVSRGARDRVRSMS.GGHGLRVGALD...VPASQFLGSATSPGPRTAPAAKPEKASAGTRVPVQEK..TNLAAYVPLLTQ......GWAEILVRRPTGNTSWLMSLENPLSPFSSDI..NNMPLQELSNALMAAERFKEHRDTALYKSLSVPAASTAKPPPLPRSNTDSAVVMEEGSPGEVPVLVEPPGLEDVEAALG.MDRRTDAYSRSSSVSSQEEKSLHAEE..LVGRGIPIERVVSSEGGRPSVDLSFQPSQPLSKSSSSPELQTLQDILGDPG.......DKADVGRLSPEVKARSQSGTLD...GESAAWSASGEDSRGQPEGPLPSSSPRSPSGLRPRGYTISDSA........PSRR.GKRVER.DALKSRATASNAEKVPGINPSFVFLQLYHSPFFGDESNKPILLPNESQSFERSVQLLDQIPSYDTHKIAVLYVG......EGQSNSELAILSNEHGSYRYTEFLTGLGRLIELKDCQPDKVYLGGLDVCGEDGQFTYCWHDDIMQAVFHIATLMPTKDVDKHRCDKKRHLGNDFVSIVYNDSGEDFKLGTIKGQFNFVHVIVTPLDYECNLVSLQCRKDMEGLVDTSVAKIVSDRNLPFVARQMALHANMASQVHHSRSNPTDIYPSKWIARLRHIKRLRQRICEEAAYSNPSLPLVHPPSHSKAPAQTPAEPTPGYEVGQRKRLISSVEDFTEFV  
s2:
.................................................................................................................................................................................................................................................................................................................................................................................MAQQANVGELLAMLDSP.MLGVRDDVTAVFKENLNS.......DRGPMLVNTLVDYYLETS.......SQPALHILTTLQEPHDKHLLDRINEYVGKAATRLSILSLLGHVIRLQPSWKHKLSQAPLLPSLLKCLKMDTDVVVLTTGVLVLITMLPMIPQSGKQHLLDFFDIFGRLSSWCLKKPGHVAEVYLVHLHASVYALFHRLYGMYPCNFVSFLRSHYSMKENLETFEEVVKPMMEHVRIHPELVTGSKDHELDPRRWKRLETHDVVIECAKISLDPTEASYEDG...YSVSHQISARFPHRSADVTTS.PYADTQNSYGCAT........STPYSTSRLMLLN.............MPGQLPQTLSSPSTRLITEPPQATLWSPSMVCGMTTPPTSPGNV...PPDLSHP..YSKVFGTTAGGKGTPLGTPATSPPPAPLCHSDDYVHISLPQATVT....PPRKEERMDSARPCLHRQHHLLNDRGSEEPPGSKGSVTLSDLPGFLGDLASEE.DSIEKDKEEAAISRELSEITTAEAEPVVPRGGFDS..PFYRDSLPGSQRKTHSAASSSQGASVNPEPLHSSLDKLG..PDT......PKQAFT...PI.DLPCGSADES......PAGDRECQTSLETSIFTPSPCKIPPPTRVGFGSGQPPPYDHLFEVALPKTAHHFVIRKTEELLKKAKGNTEEDGVPSTSPMEVLDRLIQQGADAHSKELNKLPLPSKSVDWTHFGGSPPSDEIRTLRDQLLLLHNQLLYERFKRQQHALRNRRLLRKVIKAAALEEHNAAMKDQLKLQEKDIQMWKVSLQKEQARYNQLQEQRDTMVTKLHSQIRQLQHDREEFYNQSQELQTKLEDCRNMIAELRIELKKANNKVCHTELLLSQVSQKLSNSESVQQQMEFLNRQLLVLGEVNELYLEQLQNKHSDTTKEVE.........MMKAAYRKELEKNRSHVLQQTQRLDTSQKRILELESHLAKKDHLLLEQKKYLEDVKLQARGQLQAAESRYEAQKRITQVFELEILDLYGRLEKDGLLKKLEEEKAEAAEAAEERLDCCNDGCSDSMVGHNE..EASGHN..GETKTPRPSSA.RGSSGSRGGGGSSSSSSELSTPEKPPHQRAGPFSSRWETTMGEASASIPTTVGSLPSSKSFLGMKARELFRNKSESQCDEDGMTSSLSESLKTELGKDLGVEAKIPLNLDGPHPSPPTPDSVGQLHIMDYNETHHEHS...........................................................................................................................................................................................................................................  
s1:
MDYKDDDDKAKPTSKDSGLKEKFKILLGLGTPRPNPRSAEGKQTEFIITAEILRELSMECGLNNRIRMIGQICEVAKTKKFEEHAVEALWKAVADLLQPERPLEARHAVLALLKAIVQGQGERLGVLRALFFKVIKDYPSNEDLHERLEVFKALTDNGRHITYLEEELADFVLQWMDVGLSSEFLLVLVNLVKFNSCYLDEYIARMVQMICLLCVRTASSVDIEVSLQVLDAVVCYNCLPAESLPLFIVTLCRTINVKELCEPCWKLMRNLLGTHLGHSAIYNMCHLMEDRAYMEDAPLLRGAVFFVGMALWGAHRLYSLRNSPTSVLPSFYQAMACPNEVVSYEIVLSITRLIKKYRKELQVVAWDILLNIIERLLQQLQTLDSPELRTIVHDLLTTVEELCDQNEFHGSQERYFELVERCADQRPESSLLNLISYRAQSIHPAKDGWIQNLQALMERFFRSESRGAVRIKVLDVLSFVLLINRQFYEEELINSVVISQLSHIPEDKDHQVRKLATQLLVDLAEG...CHTHHFNSLLDIIEKVMARSLSPPPELEERDVAAYSASLEDVKTAVLGLLVILQTKLYTL......PASHATRVYEMLVSHIQLHYKH.....SYTLPIASSIRLQAFDFLLLLRADSLHRLGLPNKDGVVRFSPYCVCDYMEPERGSEKKTSGPLSPPTGPPGPAPAGPAVRLGSVPYSLLFRVLLQCLKQESDWKVLKLVLGRLPESLR..YKVLIFTSPCSVDQLCSALCSMLSGPKTLERLRGAPEGFSRTDLHLAVVPVLTALISYHNYLDKTKQREMVYCLEQGLIHRCASQCVVALSICSVEMPDIIIKALPVLVVKLTHISATASMAVPLLEFLSTLARLPHLYRNFAAEQYASVFAISLPYTNPSKFNQYIVCLAHHVIAMWFIRCRLPFRKDFVPFITKGLRSNVLLSFDDTPEKDSFRARSTSLNERP..KSLRIARP..PKQGLNNSPPVKEFKESSAAEAFRCRSISVSEHVVRSRIQTSLTSASLGSADENSVAQADDSLKNLHLELTETCLDMMARYVFSNFTAVPKRSPVGEFLLAG.GRTKTWLVGNKLVTVTTSVGTGTRSLLGLDSGELQSGPESSSSPGVHVRQTKEAPAKLESQAGQQVSRGARDRVRSMS.GGHGLRVGALD...VPASQFLGSATSPGPRTAPAAKPEKASAGTRVPVQEK..TNLAAYVPLLTQ......GWAEILVRRPTGNTSWLMSLENPLSPFSSDI..NNMPLQELSNALMAAERFKEHRDTALYKSLSVPAASTAKPPPLPRSNTDSAVVMEEGSPGEVPVLVEPPGLEDVEAALG.MDRRTDAYSRSSSVSSQEEKSLHAEE..LVGRGIPIERVVSSEGGRPSVDLSFQPSQPLSKSSSSPELQTLQDILGDPG.......DKADVGRLSPEVKARSQSGTLD...GESAAWSASGEDSRGQPEGPLPSSSPRSPSGLRPRGYTISDSA........PSRR.GKRVER.DALKSRATASNAEKVPGINPSFVFLQLYHSPFFGDESNKPILLPNESQSFERSVQLLDQIPSYDTHKIAVLYVG......EGQSNSELAILSNEHGSYRYTEFLTGLGRLIELKDCQPDKVYLGGLDVCGEDGQFTYCWHDDIMQAVFHIATLMPTKDVDKHRCDKKRHLGNDFVSIVYNDSGEDFKLGTIKGQFNFVHVIVTPLDYECNLVSLQCRKDMEGLVDTSVAKIVSDRNLPFVARQMALHANMASQVHHSRSNPTDIYPSKWIARLRHIKRLRQRICEEAAYSNPSLPLVHPPSHSKAPAQTPAEPTPGYEVGQRKRLISSVEDFTEFV  
s2:
.................................................................................................................................................................................................................................................................................................................................................................................MAQQANVGELLAMLDSP.MLGVRDDVTAVFKENLNS.......DRGPMLVNTLVDYYLETS.......SQPALHILTTLQEPHDKHLLDRINEYVGKAATRLSILSLLGHVIRLQPSWKHKLSQAPLLPSLLKCLKMDTDVVVLTTGVLVLITMLPMIPQSGKQHLLDFFDIFGRLSSWCLKKPGHVAEVYLVHLHASVYALFHRLYGMYPCNFVSFLRSHYSMKENLETFEEVVKPMMEHVRIHPELVTGSKDHELDPRRWKRLETHDVVIECAKISLDPTEASYEDG...YSVSHQISARFPHRSADVTTS.PYADTQNSYGCAT........STPYSTSRLMLLN.............MPGQLPQTLSSPSTRLITEPPQATLWSPSMVCGMTTPPTSPGNV...PPDLSHP..YSKVFGTTAGGKGTPLGTPATSPPPAPLCHSDDYVHISLPQATVT....PPRKEERMDSARPCLHRQHHLLNDRGSEEPPGSKGSVTLSDLPGFLGDLASEE.DSIEKDKEEAAISRELSEITTAEAEPVVPRGGFDS..PFYRDSLPGSQRKTHSAASSS............QGASVNPEPLHSSLDKLGPDTPKQAFT...PI.DLPCGSADES......PAGDRECQTSLETSIFTPSPCKIPPPTRVGFGSGQPPPYDHLFEVALPKTAHHFVIRKTEELLKKAKGNTEEDGVPSTSPMEVLDRLIQQGADAHSKELNKLPLPSKSVDWTHFGGSPPSDEIRTLRDQLLLLHNQLLYERFKRQQHALRNRRLLRKVIKAAALEEHNAAMKDQLKLQEKDIQMWKVSLQKEQARYNQLQEQRDTMVTKLHSQIRQLQHDREEFYNQSQELQTKLEDCRNMIAELRIELKKANNKVCHTELLLSQVSQKLSNSESVQQQMEFLNRQLLVLGEVNELYLEQLQNKHSDTTKEVE.........MMKAAYRKELEKNRSHVLQQTQRLDTSQKRILELESHLAKKDHLLLEQKKYLEDVKLQARGQLQAAESRYEAQKRITQVFELEILDLYGRLEKDGLLKKLEEEKAEAAEAAEERLDCCNDGCSDSMVGHNE..EASGHN..GETKTPRPSSA.RGSSGSRGGGGSSSSSSELSTPEKPPHQRAGPFSSRWETTMGEASASIPTTVGSLPSSKSFLGMKARELFRNKSESQCDEDGMTSSLSESLKTELGKDLGVEAKIPLNLDGPHPSPPTPDSVGQLHIMDYNETHHEHS...........................................................................................................................................................................................................................................  
s1:
MAQQANVGELLAMLDSPMLGVRDDVTAVFKENLNSDRGPMLVNTLVDYYLETSSQPALHILTTLQEPHDKHLLDRINEYVGKAATRLSILSLLGHVIRLQPSWKHKLSQAPLLPSLLKCLKMDTDVVVLTTGVLVLITMLPMIPQSGKQHLLDFFDIFGRLSSWCLKKPGHVAEVYLVHLHASVYALFHRLYGMYPCNFVSFLRSHYSMKENLETFEEVVKPMMEHVRIHPELVTGSKDHELDPRRWKRLETHDVVIECAKISLDPTEASYEDGYSVSHQISARFPHRSADVTTSPYADTQNSYGCATSTPYSTSRLMLLNMPGQLPQTLSSPSTRLITEPPQATLWSPSMVCGMTTPPTSPGNVPPDLSHPYSKVFGTTAGGKGTPLGTPATSPPPAPLCHSDDYVHISLPQATVTPPRKEERMDSARPCLHRQHHLLNDRGSEEPPGSKGSVTLSDLPGFLGDLASEEDSIEKDKEEAAISRELSEITTAEAEPVVPRGGFDSPFYRDSLPGSQRKTHSAASSSQGASVNPEPLHSSLDKLGPDTPKQAFTPIDLPCGSADESPAGDRECQTSLETSIFTPSPCKIPPPTRVGFGSGQPPPYDHLFEVALPKTAHHFVIRKTEELLKKAKGNTEEDGVPSTSPMEVLDRLIQQGADAHSKELNKLPLPSKSVDWTHFGGSPPSDEIRTLRDQLLLLHNQLLYERFKRQQHALRNRRLLRKVIKAAALEEHNAAMKDQLKLQEKDIQMWKVSLQKEQARYNQLQEQRDTMVTKLHSQIRQLQHDREEFYNQSQELQTKLEDCRNMIAELRIELKKANNKVCHTELLLSQVSQKLSNSESVQQQMEFLNRQLLVLGEVNELYLEQLQNKHSDTTKEVEMMKAAYRKELEKNRSHVLQQTQRLDTSQKRILELESHLAKKDHLLLEQKKYLEDVKLQARGQLQAAESRYEAQKRITQVFELEILDLYGRLEKDGLLKKLEEEKAEAAEAAEERLDCCNDGCSDSMVGHNEEASGHNGETKTPRPSSARGSSGSRGGGGSSSSSSELSTPEKPPHQRAGPFSSRWETTMGEASASIPTTVGSLPSSKSFLGMKARELFRNKSESQCDEDGMTSSLSESLKTELGKDLGVEAKIPLNLDGPHPSPPTPDSVGQLHIMDYNETHHEHSGTKLGPEQKLISEEDLNSAVDHHHHHH  
s2:
MAQQANVGELLAMLDSPMLGVRDDVTAVFKENLNSDRGPMLVNTLVDYYLETSSQPALHILTTLQEPHDKHLLDRINEYVGKAATRLSILSLLGHVIRLQPSWKHKLSQAPLLPSLLKCLKMDTDVVVLTTGVLVLITMLPMIPQSGKQHLLDFFDIFGRLSSWCLKKPGHVAEVYLVHLHASVYALFHRLYGMYPCNFVSFLRSHYSMKENLETFEEVVKPMMEHVRIHPELVTGSKDHELDPRRWKRLETHDVVIECAKISLDPTEASYEDGYSVSHQISARFPHRSADVTTSPYADTQNSYGCATSTPYSTSRLMLLNMPGQLPQTLSSPSTRLITEPPQATLWSPSMVCGMTTPPTSPGNVPPDLSHPYSKVFGTTAGGKGTPLGTPATSPPPAPLCHSDDYVHISLPQATVTPPRKEERMDSARPCLHRQHHLLNDRGSEEPPGSKGSVTLSDLPGFLGDLASEEDSIEKDKEEAAISRELSEITTAEAEPVVPRGGFDSPFYRDSLPGSQRKTHSAASSSQGASVNPEPLHSSLDKLGPDTPKQAFTPIDLPCGSADESPAGDRECQTSLETSIFTPSPCKIPPPTRVGFGSGQPPPYDHLFEVALPKTAHHFVIRKTEELLKKAKGNTEEDGVPSTSPMEVLDRLIQQGADAHSKELNKLPLPSKSVDWTHFGGSPPSDEIRTLRDQLLLLHNQLLYERFKRQQHALRNRRLLRKVIKAAALEEHNAAMKDQLKLQEKDIQMWKVSLQKEQARYNQLQEQRDTMVTKLHSQIRQLQHDREEFYNQSQELQTKLEDCRNMIAELRIELKKANNKVCHTELLLSQVSQKLSNSESVQQQMEFLNRQLLVLGEVNELYLEQLQNKHSDTTKEVEMMKAAYRKELEKNRSHVLQQTQRLDTSQKRILELESHLAKKDHLLLEQKKYLEDVKLQARGQLQAAESRYEAQKRITQVFELEILDLYGRLEKDGLLKKLEEEKAEAAEAAEERLDCCNDGCSDSMVGHNEEASGHNGETKTPRPSSARGSSGSRGGGGSSSSSSELSTPEKPPHQRAGPFSSRWETTMGEASASIPTTVGSLPSSKSFLGMKARELFRNKSESQCDEDGMTSSLSESLKTELGKDLGVEAKIPLNLDGPHPSPPTPDSVGQLHIMDYNETHHEHS...........................  
s1:
MAQQANVGELLAMLDSPMLGVRDDVTAVFKENLNSDRGPMLVNTLVDYYLETSSQPALHILTTLQEPHDKHLLDRINEYVGKAATRLSILSLLGHVIRLQPSWKHKLSQAPLLPSLLKCLKMDTDVVVLTTGVLVLITMLPMIPQSGKQHLLDFFDIFGRLSSWCLKKPGHVAEVYLVHLHASVYALFHRLYGMYPCNFVSFLRSHYSMKENLETFEEVVKPMMEHVRIHPELVTGSKDHELDPRRWKRLETHDVVIECAKISLDPTEASYEDGYSVSHQISARFPHRSADVTTSPYADTQNSYGCATSTPYSTSRLMLLNMPGQLPQTLSSPSTRLITEPPQATLWSPSMVCGMTTPPTSPGNVPPDLSHPYSKVFGTTAGGKGTPLGTPATSPPPAPLCHSDDYVHISLPQATVTPPRKEERMDSARPCLHRQHHLLNDRGSEEPPGSKGSVTLSDLPGFLGDLASEEDSIEKDKEEAAISRELSEITTAEAEPVVPRGGFDSPFYRDSLPGSQRKTHSAASSSQGASVNPEPLHSSLDKLGPDTPKQAFTPIDLPCGSADESPAGDRECQTSLETSIFTPSPCKIPPPTRVGFGSGQPPPYDHLFEVALPKTAHHFVIRKTEELLKKAKGNTEEDGVPSTSPMEVLDRLIQQGADAHSKELNKLPLPSKSVDWTHFGGSPPSDEIRTLRDQLLLLHNQLLYERFKRQQHALRNRRLLRKVIKAAALEEHNAAMKDQLKLQEKDIQMWKVSLQKEQARYNQLQEQRDTMVTKLHSQIRQLQHDREEFYNQSQELQTKLEDCRNMIAELRIELKKANNKVCHTELLLSQVSQKLSNSESVQQQMEFLNRQLLVLGEVNELYLEQLQNKHSDTTKEVEMMKAAYRKELEKNRSHVLQQTQRLDTSQKRILELESHLAKKDHLLLEQKKYLEDVKLQARGQLQAAESRYEAQKRITQVFELEILDLYGRLEKDGLLKKLEEEKAEAAEAAEERLDCCNDGCSDSMVGHNEEASGHNGETKTPRPSSARGSSGSRGGGGSSSSSSELSTPEKPPHQRAGPFSSRWETTMGEASASIPTTVGSLPSSKSFLGMKARELFRNKSESQCDEDGMTSSLSESLKTELGKDLGVEAKIPLNLDGPHPSPPTPDSVGQLHIMDYNETHHEHSGTKLGPEQKLISEEDLNSAVDHHHHHH  
s2:
MAQQANVGELLAMLDSPMLGVRDDVTAVFKENLNSDRGPMLVNTLVDYYLETSSQPALHILTTLQEPHDKHLLDRINEYVGKAATRLSILSLLGHVIRLQPSWKHKLSQAPLLPSLLKCLKMDTDVVVLTTGVLVLITMLPMIPQSGKQHLLDFFDIFGRLSSWCLKKPGHVAEVYLVHLHASVYALFHRLYGMYPCNFVSFLRSHYSMKENLETFEEVVKPMMEHVRIHPELVTGSKDHELDPRRWKRLETHDVVIECAKISLDPTEASYEDGYSVSHQISARFPHRSADVTTSPYADTQNSYGCATSTPYSTSRLMLLNMPGQLPQTLSSPSTRLITEPPQATLWSPSMVCGMTTPPTSPGNVPPDLSHPYSKVFGTTAGGKGTPLGTPATSPPPAPLCHSDDYVHISLPQATVTPPRKEERMDSARPCLHRQHHLLNDRGSEEPPGSKGSVTLSDLPGFLGDLASEEDSIEKDKEEAAISRELSEITTAEAEPVVPRGGFDSPFYRDSLPGSQRKTHSAASSSQGASVNPEPLHSSLDKLGPDTPKQAFTPIDLPCGSADESPAGDRECQTSLETSIFTPSPCKIPPPTRVGFGSGQPPPYDHLFEVALPKTAHHFVIRKTEELLKKAKGNTEEDGVPSTSPMEVLDRLIQQGADAHSKELNKLPLPSKSVDWTHFGGSPPSDEIRTLRDQLLLLHNQLLYERFKRQQHALRNRRLLRKVIKAAALEEHNAAMKDQLKLQEKDIQMWKVSLQKEQARYNQLQEQRDTMVTKLHSQIRQLQHDREEFYNQSQELQTKLEDCRNMIAELRIELKKANNKVCHTELLLSQVSQKLSNSESVQQQMEFLNRQLLVLGEVNELYLEQLQNKHSDTTKEVEMMKAAYRKELEKNRSHVLQQTQRLDTSQKRILELESHLAKKDHLLLEQKKYLEDVKLQARGQLQAAESRYEAQKRITQVFELEILDLYGRLEKDGLLKKLEEEKAEAAEAAEERLDCCNDGCSDSMVGHNEEASGHNGETKTPRPSSARGSSGSRGGGGSSSSSSELSTPEKPPHQRAGPFSSRWETTMGEASASIPTTVGSLPSSKSFLGMKARELFRNKSESQCDEDGMTSSLSESLKTELGKDLGVEAKIPLNLDGPHPSPPTPDSVGQLHIMDYNETHHEHS...........................  
s1:
....................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................MTEDSQRNFR....SVYYEKVGFRGVEEKKSLEILLKDDRLDTEKLCTFSQRF.PLPSMYRALVWKVLLGI..LPPHHESHAKVMMYRKEQYLDVLHALKVVRFVSDATPQAEVYLRMYQLE.SGKLPRSPSF..PLEPDDEVFLAIAKAMEEMVEDSVDCYWITRRFVNQLNTKYRDSLPQLPKAFEQYLNLEDGRLLTHLRMCSAAPKLPYDLWFKRCFAGC..LPESSLQRVWDKVVSGSCKILVFVAVEILLTF..........KIKVMALNSAEKITKFLENIPQDSSDAIVSKAIDLWHKHCG...TPVHSSDYKDDDDK...................................................................................................................................  
s2:
MAQQANVGELLAMLDSPMLGVRDDVTAVFKENLNSDRGPMLVNTLVDYYLETSSQPALHILTTLQEPHDKHLLDRINEYVGKAATRLSILSLLGHVIRLQPSWKHKLSQAPLLPSLLKCLKMDTDVVVLTTGVLVLITMLPMIPQSGKQHLLDFFDIFGRLSSWCLKKPGHVAEVYLVHLHASVYALFHRLYGMYPCNFVSFLRSHYSMKENLETFEEVVKPMMEHVRIHPELVTGSKDHELDPRRWKRLETHDVVIECAKISLDPTEASYEDGYSVSHQISARFPHRSADVTTSPYADTQNSYGCATSTPYSTSRLMLLNMPGQLPQTLSSPSTRLITEPPQATLWSPSMVCGMTTPPTSPGNVPPDLSHPYSKVFGTTAGGKGTPLGTPATSPPPAPLCHSDDYVHISLPQATVTPPRKEERMDSARPCLHRQHHLLNDRGSEEPPGSKGSVTLSDLPGFLGDLASEEDSIEKDKEEAAISRELSEITTAEAEPVVPRGGFDSPFYRDSLPGSQRKTHSAASSSQGASVNPEPLHSSLDKLGPDTPKQAFTPIDLPCGSADESPAGDRECQTSLETSIFTPSPCKIPPPTRVGFGSGQPPPYDHLFEVALPKTAHHFVIRKTEELLKKAKGNTEEDGVPSTSPMEVLDRLIQQGADAHSKELNKLPLPSKSVDWTHFGGSPPSDEIRTLRDQLLLLHNQLLYERFKRQQHALRNRRLLRKVIKAAALEEHNAAMKDQLKLQEKDIQMWKVSLQKEQARYNQLQEQRDTMVTKLHSQIRQLQHDREEFYNQSQELQTKLEDCRNMIAELRIELKKANNKVCHTELLLSQVSQKLSNSESVQQQMEFLNRQLLVLGEVNELYLEQLQNKHSDTTKEVEMMKAAYRKELEKNRSHVLQQTQRLDTSQKRILELESHLAKKDHLLLEQKKYLEDVKLQARGQLQAAESRYEAQKRITQVFELEILDLYGRLEKDGLLKKLEEEKAEAAEAAEERLDCCNDGCSDSMVGHNEEA.SGHNGETKTPRPSSARGSSGSRGGGGSSSSSSELSTPEKPPHQRAGPFSSRWETTMGEASASIPTTVGSLPSSKSFLGMKARELFRNKSESQCDEDGMTSSLSESLKTELGKDLGVEAKIPLNLDGPHPSPPTPDSVGQLHIMDYNETHHEHS  
s1:
..............................................................................................................................................................................MHHHHHHGLLYAGFNQDHGCFACGMENGFRVYNTDPLKEKEKQEFLEGGVGHVEMLFRCNYLALVGGGKKKVMIWDDLKKKTVIEIEFSTEVKAVKLRRDRIVVVLDSMIKVFTFTHNPH.QLHVFETCY....NPKGLCVLCPNSNN..SLLAFPGTHTGHVQLVDLASTEKPPVDIPAHEGVLSCIALNLQGTRIATASEKGTLIRIFDTSSGHLIQELRRGSQAANIYCINFNQDASLICVSSDHGTVHIFAAEDPKSKWSFSKFQVPSGSPCICAFGTEPNAVIAICADGSYYKFLFNPKGECIRDVYAQFLEMTDDKL..............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................  
s2:
MAQQANVGELLAMLDSPMLGVRDDVTAVFKENLNSDRGPMLVNTLVDYYLETSSQPALHILTTLQEPHDKHLLDRINEYVGKAATRLSILSLLGHVIRLQPSWKHKLSQAPLLPSLLKCLKMDTDVVVLTTGVLVLITMLPMIPQSGKQHLLDFFDIFGRLSSWCLKKPGHVAEVYLVHLHASVYALFHRLYGMYPCNFVSFLRSHYSMKENLETFEEVVKPMMEHVRI.....HPELVTGSKDHEL..DPRRWKRLETHDVVIECAKISLDPTEASYEDGYSVSHQISARFPHRSADVTTSPYADTQNSYGCATSTPYSTSRLMLLNMPGQLPQTLSSPSTRLITEPPQATLWSPSMVCGMTTPPTSPGNVPPDLSHPYSKVFGTTAGGKGTPL..GTPAT.......SPPPAPLCHSDDY..VHISLPQATVTP.PRKEERMDSARPCLHRQHHLLNDRGSEEPPGSKGSVTLSDLPGFLGDLASEEDSIEKDKEEAAISRELSEITTAEAEPVVPRGGFDSPFYRDSLPGSQRKTHSAASSSQGASVNPEPLHSSLDKLGPDTPKQAFTPIDLPCGSADESPAGDRECQTSLETSIFTPSPCKIPPPTRVGFGSGQPPPYDHLFEVALPKTAHHFVIRKTEELLKKAKGNTEEDGVPSTSPMEVLDRLIQQGADAHSKELNKLPLPSKSVDWTHFGGSPPSDEIRTLRDQLLLLHNQLLYERFKRQQHALRNRRLLRKVIKAAALEEHNAAMKDQLKLQEKDIQMWKVSLQKEQARYNQLQEQRDTMVTKLHSQIRQLQHDREEFYNQSQELQTKLEDCRNMIAELRIELKKANNKVCHTELLLSQVSQKLSNSESVQQQMEFLNRQLLVLGEVNELYLEQLQNKHSDTTKEVEMMKAAYRKELEKNRSHVLQQTQRLDTSQKRILELESHLAKKDHLLLEQKKYLEDVKLQARGQLQAAESRYEAQKRITQVFELEILDLYGRLEKDGLLKKLEEEKAEAAEAAEERLDCCNDGCSDSMVGHNEEASGHNGETKTPRPSSARGSSGSRGGGGSSSSSSELSTPEKPPHQRAGPFSSRWETTMGEASASIPTTVGSLPSSKSFLGMKARELFRNKSESQCDEDGMTSSLSESLKTELGKDLGVEAKIPLNLDGPHPSPPTPDSVGQLHIMDYNETHHEHS  
s1:
................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................????????????  
s2:
MAQQANVGELLAMLDSPMLGVRDDVTAVFKENLNSDRGPMLVNTLVDYYLETSSQPALHILTTLQEPHDKHLLDRINEYVGKAATRLSILSLLGHVIRLQPSWKHKLSQAPLLPSLLKCLKMDTDVVVLTTGVLVLITMLPMIPQSGKQHLLDFFDIFGRLSSWCLKKPGHVAEVYLVHLHASVYALFHRLYGMYPCNFVSFLRSHYSMKENLETFEEVVKPMMEHVRIHPELVTGSKDHELDPRRWKRLETHDVVIECAKISLDPTEASYEDGYSVSHQISARFPHRSADVTTSPYADTQNSYGCATSTPYSTSRLMLLNMPGQLPQTLSSPSTRLITEPPQATLWSPSMVCGMTTPPTSPGNVPPDLSHPYSKVFGTTAGGKGTPLGTPATSPPPAPLCHSDDYVHISLPQATVTPPRKEERMDSARPCLHRQHHLLNDRGSEEPPGSKGSVTLSDLPGFLGDLASEEDSIEKDKEEAAISRELSEITTAEAEPVVPRGGFDSPFYRDSLPGSQRKTHSAASSSQGASVNPEPLHSSLDKLGPDTPKQAFTPIDLPCGSADESPAGDRECQTSLETSIFTPSPCKIPPPTRVGFGSGQPPPYDHLFEVALPKTAHHFVIRKTEELLKKAKGNTEEDGVPSTSPMEVLDRLIQQGADAHSKELNKLPLPSKSVDWTHFGGSPPSDEIRTLRDQLLLLHNQLLYERFKRQQHALRNRRLLRKVIKAAALEEHNAAMKDQLKLQEKDIQMWKVSLQKEQARYNQLQEQRDTMVTKLHSQIRQLQHDREEFYNQSQELQTKLEDCRNMIAELRIELKKANNKVCHTELLLSQVSQKLSNSESVQQQMEFLNRQLLVLGEVNELYLEQLQNKHSDTTKEVEMMKAAYRKELEKNRSHVLQQTQRLDTSQKRILELESHLAKKDHLLLEQKKYLEDVKLQARGQLQAAESRYEAQKRITQVFELEILDLYGRLEKDGLLKKLEEEKAEAAEAAEERLDCCNDGCSDSMVGHNEEASGHNGETKTPRPSSARGSSGSRGGGGSSSSSSELSTPEKPPHQRAGPFSSRWETTMGEASASIPTTVGSLPSSKSFLGMKARELFRNKSESQCDEDGMTSSLSESLKTELGKDLGVEAKIPLNLDGPHPSPPTPDSVGQLHIMDYNETHHEHS  
s1:
................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................????????????  
s2:
MAQQANVGELLAMLDSPMLGVRDDVTAVFKENLNSDRGPMLVNTLVDYYLETSSQPALHILTTLQEPHDKHLLDRINEYVGKAATRLSILSLLGHVIRLQPSWKHKLSQAPLLPSLLKCLKMDTDVVVLTTGVLVLITMLPMIPQSGKQHLLDFFDIFGRLSSWCLKKPGHVAEVYLVHLHASVYALFHRLYGMYPCNFVSFLRSHYSMKENLETFEEVVKPMMEHVRIHPELVTGSKDHELDPRRWKRLETHDVVIECAKISLDPTEASYEDGYSVSHQISARFPHRSADVTTSPYADTQNSYGCATSTPYSTSRLMLLNMPGQLPQTLSSPSTRLITEPPQATLWSPSMVCGMTTPPTSPGNVPPDLSHPYSKVFGTTAGGKGTPLGTPATSPPPAPLCHSDDYVHISLPQATVTPPRKEERMDSARPCLHRQHHLLNDRGSEEPPGSKGSVTLSDLPGFLGDLASEEDSIEKDKEEAAISRELSEITTAEAEPVVPRGGFDSPFYRDSLPGSQRKTHSAASSSQGASVNPEPLHSSLDKLGPDTPKQAFTPIDLPCGSADESPAGDRECQTSLETSIFTPSPCKIPPPTRVGFGSGQPPPYDHLFEVALPKTAHHFVIRKTEELLKKAKGNTEEDGVPSTSPMEVLDRLIQQGADAHSKELNKLPLPSKSVDWTHFGGSPPSDEIRTLRDQLLLLHNQLLYERFKRQQHALRNRRLLRKVIKAAALEEHNAAMKDQLKLQEKDIQMWKVSLQKEQARYNQLQEQRDTMVTKLHSQIRQLQHDREEFYNQSQELQTKLEDCRNMIAELRIELKKANNKVCHTELLLSQVSQKLSNSESVQQQMEFLNRQLLVLGEVNELYLEQLQNKHSDTTKEVEMMKAAYRKELEKNRSHVLQQTQRLDTSQKRILELESHLAKKDHLLLEQKKYLEDVKLQARGQLQAAESRYEAQKRITQVFELEILDLYGRLEKDGLLKKLEEEKAEAAEAAEERLDCCNDGCSDSMVGHNEEASGHNGETKTPRPSSARGSSGSRGGGGSSSSSSELSTPEKPPHQRAGPFSSRWETTMGEASASIPTTVGSLPSSKSFLGMKARELFRNKSESQCDEDGMTSSLSESLKTELGKDLGVEAKIPLNLDGPHPSPPTPDSVGQLHIMDYNETHHEHS  

> select clear

> isolde restrain distances "#1.2/C" templateAtoms "#2.3/C" perChain false
> adjustForConfidence true useCoordinateAlignment false kappa 4.40 fallOff
> 2.50 groupName "Reference Distance Restraints"

ISOLDE: Checking and correcting nomenclature for (pseudo)symmetric side
chains...  
[Repeated 1 time(s)]ISOLDE: Corrected atom nomenclature of 178 residues in
model #2.3 to IUPAC-IUB standards.  
Computing secondary structure  
[Repeated 1 time(s)]

> isolde restrain torsions #1.2/C templateResidues #2.3/C adjustForConfidence
> true sidechains true springConstant 250.00 alpha 0.20

ISOLDE: Checking and correcting nomenclature for (pseudo)symmetric side
chains...  
[Repeated 1 time(s)]Computing secondary structure  
[Repeated 1 time(s)]

> isolde restrain distances "#1.2/D" templateAtoms "#2.3/C" perChain false
> adjustForConfidence true useCoordinateAlignment false kappa 4.40 fallOff
> 2.50 groupName "Reference Distance Restraints"

ISOLDE: Checking and correcting nomenclature for (pseudo)symmetric side
chains...  
[Repeated 1 time(s)]Computing secondary structure  
[Repeated 1 time(s)]

> isolde restrain torsions #1.2/C templateResidues #2.3/C adjustForConfidence
> true sidechains true springConstant 250.00 alpha 0.20

ISOLDE: Checking and correcting nomenclature for (pseudo)symmetric side
chains...  
[Repeated 1 time(s)]Computing secondary structure  
[Repeated 1 time(s)]

> isolde restrain torsions #1.2/D templateResidues #2.3/C adjustForConfidence
> true sidechains true springConstant 250.00 alpha 0.20

ISOLDE: Checking and correcting nomenclature for (pseudo)symmetric side
chains...  
[Repeated 1 time(s)]Computing secondary structure  
[Repeated 1 time(s)]

> isolde restrain distances "#1.2/D" templateAtoms "#2.3/C" perChain false
> adjustForConfidence true useCoordinateAlignment false kappa 4.40 fallOff
> 2.50 groupName "Reference Distance Restraints"

ISOLDE: Checking and correcting nomenclature for (pseudo)symmetric side
chains...  
[Repeated 1 time(s)]Computing secondary structure  
[Repeated 1 time(s)]

> isolde restrain torsions #1.2/D templateResidues #2.3/C adjustForConfidence
> true sidechains true springConstant 250.00 alpha 0.20

ISOLDE: Checking and correcting nomenclature for (pseudo)symmetric side
chains...  
[Repeated 1 time(s)]Computing secondary structure  
[Repeated 1 time(s)]

> matchmaker #2.5 to #1.2

Computing secondary structure  
[Repeated 1 time(s)]  Parameters  
---  
Chain pairing | bb  
Alignment algorithm | Needleman-Wunsch  
Similarity matrix | BLOSUM-62  
SS fraction | 0.3  
Gap open (HH/SS/other) | 18/18/6  
Gap extend | 1  
SS matrix |  |  | H | S | O  
---|---|---|---  
H | 6 | -9 | -6  
S |  | 6 | -6  
O |  |  | 4  
Iteration cutoff | 2  
  
Matchmaker 9ce3, chain E (#1.2) with AlphaFold TBCD7_HUMAN chain E, chain E
(#2.5), sequence alignment score = 1492.1  
RMSD between 271 pruned atom pairs is 0.526 angstroms; (across all 276 pairs:
0.763)  
  

> color #2.5 bychain

> color #2.5 byhetero

> color modify #2.5 hue + 50

ISOLDE: attempting to load PAE matrix for model #2.5 from the AlphaFold-EBI
database. If this fails or you wish to use a different PAE matrix, use the
"Load PAE matrix" button in ISOLDE's reference model restraints widget.  

> alphafold pae #2.5 uniprotId Q9P0N9 plot false

Fetching compressed AlphaFold PAE Q9P0N9 from
https://alphafold.ebi.ac.uk/files/AF-Q9P0N9-F1-predicted_aligned_error_v4.json  
Computing secondary structure  
[Repeated 1 time(s)]s1:
MDYKDDDDKAKPTSKDSGLKEKFKILLGLGTPRPNPRSAEGKQTEFIITAEILRELSMECGLNNRIRMIGQICEVAKTKKFEEHAVEALWKAVADLLQP.............ERPLEARHAVLALLKAIVQGQGERLGVLRALFFKVIKDYPSNED..LHERLEVFKALTDNGRHITYLEEELADFVLQWMDVG.LSSEFLLVLVNLVKFNSCYLDEYIARMVQMICLLCVRTASSVDIEVSLQVLDAVVCY.NCLPAESLPLFIVTLCRTINVKELCEPCWKLMRNLLGTHLGHSAIYNMCHLMEDRAYMEDAPLLRGAVFFVGMALWGAHRLYSLRNSPTSVLPSFYQAMACPNEVVSYEIVLSITRLIKKYRKELQVVAWDILLNIIERLLQQLQTLDSPELRTIVHDLLTTVEELCDQNEFHGSQERYFELVERCADQRPESSLLNLISYRAQSIHPAKDGWIQNLQALMERFFRSESRGAVRIKVLDVLSFVLLINRQFYEEELINSVVISQLSHIPEDKDHQVRKLATQLLVDLAEGCHTHHFNSLLDIIEKVMARSLSPPPELEERDVAAYSASLEDVKTAVLGLLVILQTKLYTLPASHATRVYEMLVSHIQLHYKHSYTLPIASSIRLQAFDFLLLLRADSLHRLGLPNKDGVVRFSPYCVCDYMEPERGSEKKTSGPLSPPTGPPGPAPAGPAVRLGSVPYSLLFRVLLQCLKQESDWKVLKLVLGRLPESLRYKVLIFTSPCSVDQLCSALCSMLSGPKTLERLRGAPEGFSRTDLHLAVVPVLTALISYHNYLDKTKQREMVYCLEQGLIHRCASQCVVALSICSVEMPDIIIKALPVLVVKLTHISATASMAVPLLEFLSTLARLPHLYRNFAAEQYASVFAISLPYTNPSKFNQYIVCLAHHVIAMWFIRCRLPFRKDFVPFITKGLRSNVLLSFDDTPEKDSFRARSTSLNERPKSLRIARPPKQGLNNSPPVKEFKESSAAEAFRCRSISVSEHVVRSRIQTSLTSASLGSADENSVAQADDSLKNLHLELTETCLDMMARYVFSNFTAVPKRSPVGEFLLAGGRTKTWLVGNKLVTVTTSVGTGTRSLLGLDSGELQSGPESSSSPGVHVRQTKEAPAKLESQAGQQVSRGARDRVRSMSGGHGLRVGALDVPASQFLGSATSPGPRTAPAAKPEKASAGTRVPVQEKTNLAAYVPLLTQGWAEILVRRPTGNTSWLMSLENPLSPFSSDINNMPLQELSNALMAAERFKEHRDTALYKSLSVPAASTAKPPPLPRSNTDSAVVMEEGSPGEVPVLVEPPGLEDVEAALGMDRRTDAYSRSSSVSSQEEKSLHAEELVGRGIPIERVVSSEGGRPSVDLSFQPSQPLSKSSSSPELQTLQDILGDPGDKADVGRLSPEVKARSQSGTLDGESAAWSASGEDSRGQPEGPLPSSSPRSPSGLRPRGYTISDSAPSRRGKRVERDALKSRATASNAEKVPGINPSFVFLQLYHSPFFGDESNKPILLPNESQSFERSVQLLDQIPSYDTHKIAVLYVGEGQSNSELAILSNEHGSYRYTEFLTGLGRLIELKDCQPDKVYLGGLDVCGEDGQFTYCWHDDIMQAVFHIATLMPTKDVDKHRCDKKRHLGNDFVSIVYNDSGEDFKLGTIKGQFNFVHVIVTPLDYECNLVSLQCRKDMEGLVDTSVAKIVSDRNLPFVARQMALHANMASQVHHSRSNPTDIYPSKWIARLRHIKRLRQRICEEAAYSNPSLPLVHPPSHSKAPAQTPAEPTPGYEVGQRKRLISSVEDFTEFV  
s2:
..............................MTEDSQRNFRSVYYEKVGFRGVEEKKSLEILLKDDRLDTEKLCTFSQRFPLPSMYRALVWKVLLGILPPHHESHAKVMMYRKEQYLDVLHALKVV..RFVSDATPQAEVYLRMYQLESGKLPRSPSFPLEPDDEVFLAIAKAMEEM..VEDSVDCYWITRRFVNQLNTKYRDSLPQLPKAFEQYLNLEDGRLLTHLRMCSAAPKLPYDLWFKR.......CFAGCLPESSLQRVWDKVV.SGSCKILVFVAVEILLTFKIKVMALNSAEKITKFLEN..IPQDS...SDAIVSKAIDLWHKHCGTPVHSS.............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................  
s1:
MDYKDDDDKAKPTSKDSGLKEKFKILLGLGTPRPNPRSAEGKQTEFIITAEILRELSMECGLNNRIRMIGQICEVAKTKKFEEHAVEALWKAVADLLQP.............ERPLEARHAVLALLKAIVQGQGERLGVLRALFFKVIKDYPSNED..LHERLEVFKALTDNGRHITYLEEELADFVLQWMDVG.LSSEFLLVLVNLVKFNSCYLDEYIARMVQMICLLCVRTASSVDIEVSLQVLDAVVCY.NCLPAESLPLFIVTLCRTINVKELCEPCWKLMRNLLGTHLGHSAIYNMCHLMEDRAYMEDAPLLRGAVFFVGMALWGAHRLYSLRNSPTSVLPSFYQAMACPNEVVSYEIVLSITRLIKKYRKELQVVAWDILLNIIERLLQQLQTLDSPELRTIVHDLLTTVEELCDQNEFHGSQERYFELVERCADQRPESSLLNLISYRAQSIHPAKDGWIQNLQALMERFFRSESRGAVRIKVLDVLSFVLLINRQFYEEELINSVVISQLSHIPEDKDHQVRKLATQLLVDLAEGCHTHHFNSLLDIIEKVMARSLSPPPELEERDVAAYSASLEDVKTAVLGLLVILQTKLYTLPASHATRVYEMLVSHIQLHYKHSYTLPIASSIRLQAFDFLLLLRADSLHRLGLPNKDGVVRFSPYCVCDYMEPERGSEKKTSGPLSPPTGPPGPAPAGPAVRLGSVPYSLLFRVLLQCLKQESDWKVLKLVLGRLPESLRYKVLIFTSPCSVDQLCSALCSMLSGPKTLERLRGAPEGFSRTDLHLAVVPVLTALISYHNYLDKTKQREMVYCLEQGLIHRCASQCVVALSICSVEMPDIIIKALPVLVVKLTHISATASMAVPLLEFLSTLARLPHLYRNFAAEQYASVFAISLPYTNPSKFNQYIVCLAHHVIAMWFIRCRLPFRKDFVPFITKGLRSNVLLSFDDTPEKDSFRARSTSLNERPKSLRIARPPKQGLNNSPPVKEFKESSAAEAFRCRSISVSEHVVRSRIQTSLTSASLGSADENSVAQADDSLKNLHLELTETCLDMMARYVFSNFTAVPKRSPVGEFLLAGGRTKTWLVGNKLVTVTTSVGTGTRSLLGLDSGELQSGPESSSSPGVHVRQTKEAPAKLESQAGQQVSRGARDRVRSMSGGHGLRVGALDVPASQFLGSATSPGPRTAPAAKPEKASAGTRVPVQEKTNLAAYVPLLTQGWAEILVRRPTGNTSWLMSLENPLSPFSSDINNMPLQELSNALMAAERFKEHRDTALYKSLSVPAASTAKPPPLPRSNTDSAVVMEEGSPGEVPVLVEPPGLEDVEAALGMDRRTDAYSRSSSVSSQEEKSLHAEELVGRGIPIERVVSSEGGRPSVDLSFQPSQPLSKSSSSPELQTLQDILGDPGDKADVGRLSPEVKARSQSGTLDGESAAWSASGEDSRGQPEGPLPSSSPRSPSGLRPRGYTISDSAPSRRGKRVERDALKSRATASNAEKVPGINPSFVFLQLYHSPFFGDESNKPILLPNESQSFERSVQLLDQIPSYDTHKIAVLYVGEGQSNSELAILSNEHGSYRYTEFLTGLGRLIELKDCQPDKVYLGGLDVCGEDGQFTYCWHDDIMQAVFHIATLMPTKDVDKHRCDKKRHLGNDFVSIVYNDSGEDFKLGTIKGQFNFVHVIVTPLDYECNLVSLQCRKDMEGLVDTSVAKIVSDRNLPFVARQMALHANMASQVHHSRSNPTDIYPSKWIARLRHIKRLRQRICEEAAYSNPSLPLVHPPSHSKAPAQTPAEPTPGYEVGQRKRLISSVEDFTEFV  
s2:
..............................MTEDSQRNFRSVYYEKVGFRGVEEKKSLEILLKDDRLDTEKLCTFSQRFPLPSMYRALVWKVLLGILPPHHESHAKVMMYRKEQYLDVLHALKVV..RFVSDATPQAEVYLRMYQLESGKLPRSPSFPLEPDDEVFLAIAKAMEEM..VEDSVDCYWITRRFVNQLNTKYRDSLPQLPKAFEQYLNLEDGRLLTHLRMCSAAPKLPYDLWFKR.......CFAGCLPESSLQRVWDKVV.SGSCKILVFVAVEILLTFKIKVMALNSAEKITKFLEN..IPQDS...SDAIVSKAIDLWHKHCGTPVHSS.............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................  
s1:
MAQQANVGELLAMLDSPMLGVRDDVTAVFKENLNSDRGPMLVNTLVDYYLETSSQPALHILTTLQEPHDKHLLDRINEYVGKAATRLSILSLLGHVIRLQPSWKHKLSQAPLLPSLLKCLKMDTDVVVLTTGVLVLITMLPMIPQSGKQHLLDFFDIFGRLSSWCLKKPGHVAEVYLVHLHASVYALFHRLYGMYPCNFVSFLRSHYSMKENLETFEEVVKPMMEHVRIHPELVTGSKDHELDPRRWKRLETHDVVIECAKISLDPTEASYEDGYSVSHQISARFPHRSADVTTSPYADTQNSYGCATSTPYSTSRLMLLNMPGQLPQTLSSPSTRLITEPPQATLWSPSMVCGMTTPPTSPGNVPPDLSHPYSKVFGTTAGGKGTPLGTPATSPPPAPLCHSDDYVHISLPQATVTPPRKEERMDSARPCLHRQHHLLNDRGSEEPPGSKGSVTLSDLPGFLGDLASEEDSIEKDKEEAAISRELSEITTAEAEPVVPRGGFDSPFYRDSLPGSQRKTHSAASSSQGASVNPEPLHSSLDKLGPDTPKQAFTPIDLPCGSADESPAGDRECQTSLETSIFTPSPCKIPPPTRVGFGSGQPPPYDHLFEVALPKTAHHFVIRKTEELLKKAKGNTEEDGVPSTSPMEVLDRLIQQGADAHSKELNKLPLPSKSVDWTHFGGSPPSDEIRTLRDQLLLLHNQLLYERFKRQQHALRNRRLLRKVIKAAALEEHNAAMKDQLKLQEKDIQMWKVSLQKEQARYNQLQEQRDTMVTKLHSQIRQLQHDREEFYNQSQELQTKLEDCRNMIAELRIELKKANNKVCHTELLLSQVSQKLSNSESVQQQMEFLNRQLLVLGEVNELYLEQLQNKHSDTTKEVEMMKAAYRKELEKNRSHVLQQTQRLDTSQKRILELESHLAKKDHLLLEQKKYLEDVKLQARGQLQAAESRYEAQKRITQVFELEILDLYGRLE......KDGLLKKLEEEKAEAAEA.AEERLDCCNDGCSDSMVGHNEEASGHNGETKTPRPSSARGSSGSRGGGGSSSSSSELSTPEKPPHQRAGPFSSRWETTMGEASASIPTTVGSLPSSKSFLGMKARELFRNKSESQCDEDGMTSSLSESLKTELGKDLGVEAKIPLNLDGPHPSPPTPDSVGQLHIMDYNETHHEHSGTKLGPEQKLISEEDLNSAVDHHHHHH  
s2:
.......................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................MTEDSQRNFRSVYYEK.VGFRGVEEKKSLEILLKDDRLDTEKLCTFSQRF.PLPSMYRALVWKVLLGI..LPPHHESHAKVMMYRKEQYLDVLHALKVVRFVSDATPQAEVYLRMYQLE.SGKLPRSPSFP..LEPDDEVFLAIAKAMEEMVEDSVDCYWITRRFVNQLNTKYRDSLPQLPKAFEQYLNLEDGRLLTHLRMCSAAPKLPYDLWFKRCFAG..CLPESSLQRVWDKVVSGSCKILVFVAVEILLTF.KIKVMALNSAEKITKFLENIPQDSSDAIVSKAIDLWHKHCGTPV..HSS......................................................................................................................................................................................  
s1:
MAQQANVGELLAMLDSPMLGVRDDVTAVFKENLNSDRGPMLVNTLVDYYLETSSQPALHILTTLQEPHDKHLLDRINEYVGKAATRLSILSLLGHVIRLQPSWKHKLSQAPLLPSLLKCLKMDTDVVVLTTGVLVLITMLPMIPQSGKQHLLDFFDIFGRLSSWCLKKPGHVAEVYLVHLHASVYALFHRLYGMYPCNFVSFLRSHYSMKENLETFEEVVKPMMEHVRIHPELVTGSKDHELDPRRWKRLETHDVVIECAKISLDPTEASYEDGYSVSHQISARFPHRSADVTTSPYADTQNSYGCATSTPYSTSRLMLLNMPGQLPQTLSSPSTRLITEPPQATLWSPSMVCGMTTPPTSPGNVPPDLSHPYSKVFGTTAGGKGTPLGTPATSPPPAPLCHSDDYVHISLPQATVTPPRKEERMDSARPCLHRQHHLLNDRGSEEPPGSKGSVTLSDLPGFLGDLASEEDSIEKDKEEAAISRELSEITTAEAEPVVPRGGFDSPFYRDSLPGSQRKTHSAASSSQGASVNPEPLHSSLDKLGPDTPKQAFTPIDLPCGSADESPAGDRECQTSLETSIFTPSPCKIPPPTRVGFGSGQPPPYDHLFEVALPKTAHHFVIRKTEELLKKAKGNTEEDGVPSTSPMEVLDRLIQQGADAHSKELNKLPLPSKSVDWTHFGGSPPSDEIRTLRDQLLLLHNQLLYERFKRQQHALRNRRLLRKVIKAAALEEHNAAMKDQLKLQEKDIQMWKVSLQKEQARYNQLQEQRDTMVTKLHSQIRQLQHDREEFYNQSQELQTKLEDCRNMIAELRIELKKANNKVCHTELLLSQV...SQKLSNSESVQQQMEFLNRQLLVLGEVNELYLEQLQNKHSDTTKEVEMMKAAYRKELEKNRSHVLQQTQRLDTSQKRILELESHLAKKDHLLLEQKKYLEDVKLQARGQLQAAESRYEAQKRITQVFELEILDLYGRLE......KDGLLKKLEEEKAEAAEA.AEERLDCCNDGCSDSMVGHNEEASGHNGETKTPRPSSARGSSGSRGGGGSSSSSSELSTPEKPPHQRAGPFSSRWETTMGEASASIPTTVGSLPSSKSFLGMKARELFRNKSESQCDEDGMTSSLSESLKTELGKDLGVEAKIPLNLDGPHPSPPTPDSVGQLHIMDYNETHHEHSGTKLGPEQKLISEEDLNSAVDHHHHHH  
s2:
.......................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................MTEDSQRNFRSVYYEK.VGFRGVEEKKSLEILLKDDRLDTEKLCTFSQRF.PLPSMYRALVWKVLLGILP.....PHHESHAKVMMYRKEQYLDVLHALKV.VRFVSDATPQAEVYLRMYQLESGKLPRSPSFP..LEPDDEVFLAIAKAMEEMVEDSVDCYWITRRFVNQLNTKYRDSLPQLPKAFEQYLNLEDGRLLTHLRMCSAAPKLPYDLWFKRCFAG..CLPESSLQRVWDKVVSGSCKILVFVAVEILLTF.KIKVMALNSAEKITKFLENIPQDSSDAIVSKAIDLWHKHCGTPV..HSS......................................................................................................................................................................................  
s1:
MTEDSQRNFRSVYYEKVGFRGVEEKKSLEILLKDDRLDTEKLCTFSQRFPLPSMYRALVWKVLLGILPPHHESHAKVMMYRKEQYLDVLHALKVVRFVSDATPQAEVYLRMYQLESGKLPRSPSFPLEPDDEVFLAIAKAMEEMVEDSVDCYWITRRFVNQLNTKYRDSLPQLPKAFEQYLNLEDGRLLTHLRMCSAAPKLPYDLWFKRCFAGCLPESSLQRVWDKVVSGSCKILVFVAVEILLTFKIKVMALNSAEKITKFLENIPQDSSDAIVSKAIDLWHKHCGTPVHSSDYKDDDDK  
s2:
MTEDSQRNFRSVYYEKVGFRGVEEKKSLEILLKDDRLDTEKLCTFSQRFPLPSMYRALVWKVLLGILPPHHESHAKVMMYRKEQYLDVLHALKVVRFVSDATPQAEVYLRMYQLESGKLPRSPSFPLEPDDEVFLAIAKAMEEMVEDSVDCYWITRRFVNQLNTKYRDSLPQLPKAFEQYLNLEDGRLLTHLRMCSAAPKLPYDLWFKRCFAGCLPESSLQRVWDKVVSGSCKILVFVAVEILLTFKIKVMALNSAEKITKFLENIPQDSSDAIVSKAIDLWHKHCGTPVHSS........  
s1:
MHHHHHHGLLYAGFNQDHGCFACGMENGFRVYNTDP.....LKEKEKQEFLEGGVGHVEMLFRCNYLALVG.GGKKKVMIWDDLKKKTVIEIEFSTEVKAVKLRRDRIVVVLDSMIKVFTFTHNPHQLHVFETCYNPKGLCVLCPNSNNSLLAFPGTHTGHVQLVDLASTEKPPVDIPAHEGVLSCIALNLQGT.RIATASEKGTLIRIFDTSSGHLIQELRRGSQAANI.YCINFNQDASLICVSSDHGTVHIFAAEDPKSKWSFSKFQVPSGSPCICAFG......TEPNAVIAICADGSYYKFLFNPKGECIRDVYAQFLEMTDDKL.......  
s2:
....................MTEDSQRNFRSVYYEKVGFRGVEEKKSLEILLKD.DRLDTEKLCTFSQRFPLPSMYRALVWKVLLG..ILPPHHESHAKVMMYRKEQYLDVLHALKVVRFVSDATPQAEVYLRMYQLES..GKLPRSP....SFPLEPDDEVFLAIAKAMEEMVEDSVDCYWITRRFVNQLNTKYRDSLPQLPKAFEQYLNLEDGRLLTHLRMCSAAPKLPYDLWFKR.....C..........FAGCLPESSLQRVWDKVVSGSCKILVFVAVEILLTFKIKVMALNSAEKITKFLENIPQDSSDAIVSKAIDLWHKHCGTPVHSS  
s1:
.........................................................................................................................................................................................................................................................................................????????????  
s2:
MTEDSQRNFRSVYYEKVGFRGVEEKKSLEILLKDDRLDTEKLCTFSQRFPLPSMYRALVWKVLLGILPPHHESHAKVMMYRKEQYLDVLHALKVVRFVSDATPQAEVYLRMYQLESGKLPRSPSFPLEPDDEVFLAIAKAMEEMVEDSVDCYWITRRFVNQLNTKYRDSLPQLPKAFEQYLNLEDGRLLTHLRMCSAAPKLPYDLWFKRCFAGCLPESSLQRVWDKVVSGSCKILVFVAVEILLTFKIKVMALNSAEKITKFLENIPQDSSDAIVSKAIDLWHKHCGTPVHSS  
s1:
.........................................................................................................................................................................................................................................................................................????????????  
s2:
MTEDSQRNFRSVYYEKVGFRGVEEKKSLEILLKDDRLDTEKLCTFSQRFPLPSMYRALVWKVLLGILPPHHESHAKVMMYRKEQYLDVLHALKVVRFVSDATPQAEVYLRMYQLESGKLPRSPSFPLEPDDEVFLAIAKAMEEMVEDSVDCYWITRRFVNQLNTKYRDSLPQLPKAFEQYLNLEDGRLLTHLRMCSAAPKLPYDLWFKRCFAGCLPESSLQRVWDKVVSGSCKILVFVAVEILLTFKIKVMALNSAEKITKFLENIPQDSSDAIVSKAIDLWHKHCGTPVHSS  

> isolde restrain distances "#1.2/E" templateAtoms "#2.5/E" perChain false
> adjustForConfidence true useCoordinateAlignment false kappa 4.40 fallOff
> 2.50 groupName "Reference Distance Restraints"

ISOLDE: Checking and correcting nomenclature for (pseudo)symmetric side
chains...  
[Repeated 1 time(s)]ISOLDE: Corrected atom nomenclature of 47 residues in
model #2.5 to IUPAC-IUB standards.  
Computing secondary structure  
[Repeated 1 time(s)]

> isolde restrain torsions #1.2/E templateResidues #2.5/E adjustForConfidence
> true sidechains true springConstant 250.00 alpha 0.20

ISOLDE: Checking and correcting nomenclature for (pseudo)symmetric side
chains...  
[Repeated 1 time(s)]Computing secondary structure  
[Repeated 1 time(s)]

> matchmaker #2.6 to #1.2

Computing secondary structure  
[Repeated 1 time(s)]  Parameters  
---  
Chain pairing | bb  
Alignment algorithm | Needleman-Wunsch  
Similarity matrix | BLOSUM-62  
SS fraction | 0.3  
Gap open (HH/SS/other) | 18/18/6  
Gap extend | 1  
SS matrix |  |  | H | S | O  
---|---|---|---  
H | 6 | -9 | -6  
S |  | 6 | -6  
O |  |  | 4  
Iteration cutoff | 2  
  
Matchmaker 9ce3, chain F (#1.2) with AlphaFold WIPI3_HUMAN chain F, chain F
(#2.6), sequence alignment score = 1537.3  
RMSD between 287 pruned atom pairs is 0.634 angstroms; (across all 305 pairs:
1.509)  
  

> color #2.6 bychain

> color #2.6 byhetero

> color modify #2.6 hue + 50

ISOLDE: attempting to load PAE matrix for model #2.6 from the AlphaFold-EBI
database. If this fails or you wish to use a different PAE matrix, use the
"Load PAE matrix" button in ISOLDE's reference model restraints widget.  

> alphafold pae #2.6 uniprotId Q5MNZ6 plot false

Fetching compressed AlphaFold PAE Q5MNZ6 from
https://alphafold.ebi.ac.uk/files/AF-Q5MNZ6-F1-predicted_aligned_error_v4.json  
Computing secondary structure  
[Repeated 1 time(s)]s1:
MDYKDDDDKAKPTSKDSGLKEKFKILLGLGTPRPNPRSAEGKQTEFIITAEILRELSMECGLNNRIRMIGQICEVAKTKKFEEHAVEALWKAVADLLQPERPLEARHAVLALLKAIVQGQGERLGVLRALFFKVIKDYPSNEDLHERLEVFKALTDNGRHITYLEEELADFVLQWMDVGLSSEFLLVLVNLVKFNSCYLDEYIARMVQMICLLCVRTASSVDIEVSLQVLDAVVCYNCLPAESLPLFIVTLCRTINVKELCEPCWKLMRNLLGTHLGHSAIYNMCHLMED.RAYMEDAPLLRGAVFFVGMALWGAHRLYSLRNSPTSVLPSFYQAMACPNEVVSYEIVLSITRLIKKYRKELQ..VVAWDILLNIIERLLQQLQTLDSPELRTIVHDLLTTVEELCD....QNE....FHGSQERYFELVERCADQRP...ESSLLNLISYRAQSIHPAKDGWIQNLQALMERFFRSESRGAVRIKVLDVLSFVLLINRQFYEEELINSVVISQLSHIPEDKDHQVRKLATQLLVDLAEGCHTHHFNSLLDIIEKVMARSLSP........PPEL......EERDVAAYSASLEDVKTAVLGLLVILQTKLYTLPASHATRVYEMLVSHIQLHYKHSYTLPIASSIRLQAFDFLLLLRADSLHRLGLPNKDGVVRFSPYCVCDYMEPERGSEKKTSGPLSPPTGPPGPAPAGPAVRLGSVPYSLLFRVLLQCLKQESDWKVLKLVLGRLPESLRYKVLIFTSPCSVDQLCSALCSMLSGPKTLERLRGAPEGFSRTDLHLAVVPVLTALISYHNYLDKTKQREMVYCLEQGLIHRCASQCVVALSICSVEMPDIIIKALPVLVVKLTHISATASMAVPLLEFLSTLARLPHLYRNFAAEQYASVFAISLPYTNPSKFNQYIVCLAHHVIAMWFIRCRLPFRKDFVPFITKGLRSNVLLSFDDTPEKDSFRARSTSLNERPKSLRIARPPKQGLNNSPPVKEFKESSAAEAFRCRSISVSEHVVRSRIQTSLTSASLGSADENSVAQADDSLKNLHLELTETCLDMMARYVFSNFTAVPKRSPVGEFLLAGGRTKTWLVGNKLVTVTTSVGTGTRSLLGLDSGELQSGPESSSSPGVHVRQTKEAPAKLESQAGQQVSRGARDRVRSMSGGHGLRVGALDVPASQFLGSATSPGPRTAPAAKPEKASAGTRVPVQEKTNLAAYVPLLTQGWAEILVRRPTGNTSWLMSLENPLSPFSSDINNMPLQELSNALMAAERFKEHRDTALYKSLSVPAASTAKPPPLPRSNTDSAVVMEEGSPGEVPVLVEPPGLEDVEAALGMDRRTDAYSRSSSVSSQEEKSLHAEELVGRGIPIERVVSSEGGRPSVDLSFQPSQPLSKSSSSPELQTLQDILGDPGDKADVGRLSPEVKARSQSGTLDGESAAWSASGEDSRGQPEGPLPSSSPRSPSGLRPRGYTISDSAPSRRGKRVERDALKSRATASNAEKVPGINPSFVFLQLYHSPFFGDESNKPILLPNESQSFERSVQLLDQIPSYDTHKIAVLYVGEGQSNSELAILSNEHGSYRYTEFLTGLGRLIELKDCQPDKVYLGGLDVCGEDGQFTYCWHDDIMQAVFHIATLMPTKDVDKHRCDKKRHLGNDFVSIVYNDSGEDFKLGTIKGQFNFVHVIVTPLDYECNLVSLQCRKDMEGLVDTSVAKIVSDRNLPFVARQMALHANMASQVHHSRSNPTDIYPSKWIARLRHIKRLRQRICEEAAYSNPSLPLVHPPSHSKAPAQTPAEPTPGYEVGQRKRLISSVEDFTEFV  
s2:
.................................................................................................................................................................................................................................................................MNLL.PCNPHGNGLLYAGFNQDHGCFACGMENGFRVYNTDPLKEKEKQEFLEGGVGHVEMLF..RCNYLALVGGGKKPKYPPNKVMIWDDLKKKTVIEIEFSTEVKAVKLRRDRIVVVLDSMIKVFTFTHNPH.QLHVFETCYNPKGLCVLCPNSNNSLLAFPGTHTGHVQLVDLASTEKPPVDIPAHEGVLSCIALNLQGTRIATASEKGTLIRIFDTSSGHLIQELRRGSQAANIYCINFN.QDASLICVSSDHGTVHIFAAEDPKRNKQSS.....LASASFLPKYFSSKWSFSKFQVPSGSPCICAFGTEPNAVIAICADGSYYKFLFNPKGECIRDVYAQFLEMTDDKL.........................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................  
s1:
MDYKDDDDKAKPTSKDSGLKEKFKILLGLGTPRPNPRSAEGKQTEFIITAEILRELSMECGLNNRIRMIGQICEVAKTKKFEEHAVEALWKAVADLLQPERPLEARHAVLALLKAIVQGQGERLGVLRALFFKVIKDYPSNEDLHERLEVFKALTDNGRHITYLEEELADFVLQWMDVGLSSEFLLVLVNLVKFNSCYLDEYIARMVQMICLLCVRTASSVDIEVSLQVLDAVVCYNCLPAESLPLFIVTLCRTINVKELCEPCWKLMRNLLGTHLGHSAIYNMCHLMED.RAYMEDAPLLRGAVFFVGMALWGAHRLYSLRNSPTSVLPSFYQAMACPNEVVSYEIVLSITRLIKKYRKELQ..VVAWDILLNIIERLLQQLQTLDSPELRTIVHDLLTTVEELCD....QNE....FHGSQERYFELVERCADQRPE...SSLLNLISYRAQSIHPAKDGWIQNLQALMERFFRSESRGAVRIKVLDVLSFVLLINRQFYEEELINSVVISQLSHIPEDKDHQVRKLATQLLVDLAEGCHTHHFNSLLDIIEKVMARSLSP........PPEL......EERDVAAYSASLEDVKTAVLGLLVILQTKLYTLPASHATRVYEMLVSHIQLHYKHSYTLPIASSIRLQAFDFLLLLRADSLHRLGLPNKDGVVRFSPYCVCDYMEPERGSEKKTSGPLSPPTGPPGPAPAGPAVRLGSVPYSLLFRVLLQCLKQESDWKVLKLVLGRLPESLRYKVLIFTSPCSVDQLCSALCSMLSGPKTLERLRGAPEGFSRTDLHLAVVPVLTALISYHNYLDKTKQREMVYCLEQGLIHRCASQCVVALSICSVEMPDIIIKALPVLVVKLTHISATASMAVPLLEFLSTLARLPHLYRNFAAEQYASVFAISLPYTNPSKFNQYIVCLAHHVIAMWFIRCRLPFRKDFVPFITKGLRSNVLLSFDDTPEKDSFRARSTSLNERPKSLRIARPPKQGLNNSPPVKEFKESSAAEAFRCRSISVSEHVVRSRIQTSLTSASLGSADENSVAQADDSLKNLHLELTETCLDMMARYVFSNFTAVPKRSPVGEFLLAGGRTKTWLVGNKLVTVTTSVGTGTRSLLGLDSGELQSGPESSSSPGVHVRQTKEAPAKLESQAGQQVSRGARDRVRSMSGGHGLRVGALDVPASQFLGSATSPGPRTAPAAKPEKASAGTRVPVQEKTNLAAYVPLLTQGWAEILVRRPTGNTSWLMSLENPLSPFSSDINNMPLQELSNALMAAERFKEHRDTALYKSLSVPAASTAKPPPLPRSNTDSAVVMEEGSPGEVPVLVEPPGLEDVEAALGMDRRTDAYSRSSSVSSQEEKSLHAEELVGRGIPIERVVSSEGGRPSVDLSFQPSQPLSKSSSSPELQTLQDILGDPGDKADVGRLSPEVKARSQSGTLDGESAAWSASGEDSRGQPEGPLPSSSPRSPSGLRPRGYTISDSAPSRRGKRVERDALKSRATASNAEKVPGINPSFVFLQLYHSPFFGDESNKPILLPNESQSFERSVQLLDQIPSYDTHKIAVLYVGEGQSNSELAILSNEHGSYRYTEFLTGLGRLIELKDCQPDKVYLGGLDVCGEDGQFTYCWHDDIMQAVFHIATLMPTKDVDKHRCDKKRHLGNDFVSIVYNDSGEDFKLGTIKGQFNFVHVIVTPLDYECNLVSLQCRKDMEGLVDTSVAKIVSDRNLPFVARQMALHANMASQVHHSRSNPTDIYPSKWIARLRHIKRLRQRICEEAAYSNPSLPLVHPPSHSKAPAQTPAEPTPGYEVGQRKRLISSVEDFTEFV  
s2:
.................................................................................................................................................................................................................................................................MNLL.PCNPHGNGLLYAGFNQDHGCFACGMENGFRVYNTDPLKEKEKQEFLEGGVGHVEMLF..RCNYLALVGGGKKPKYPPNKVMIWDDLKKKTVIEIEFSTEVKAVKLRRDRIVVVLDSMIKVFTFTHNPH.QLHVFETCYNPKGLCVLCPNSNNSLLAFPGTHTGHVQLVDLASTEKPPVDIPAHEGVLSCIALNLQGTRIATASEKGTLIRIFDTSSGHLIQELRRGSQAANIYCINFN.QDASLICVSSDHGTVHIFAAEDPKRNKQSS.....LASASFLPKYFSSKWSFSKFQVPSGSPCICAFGTEPNAVIAICADGSYYKFLFNPKGECIRDVYAQFLEMTDDKL.........................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................  
s1:
..........................................................................MAQQANVGELLAMLDSPMLGVRDDVTAVFKENLNSDRGPMLVNTLVDYYLETSSQPALHILTTLQEPHDKHLLDRINEYVGKAATRLSILSLLGHVIRLQ.PSWKHKLSQAPLLPSLLKCLKMDTDVVVLTTGVLVLITMLPMIPQSGKQHLLDFFDIFGRLSSWCLKKPGHVAEVYLVHLHASVYALFHRLYGM...YPCNFVSFLRSHYSMKENLETFEEVVKPMMEHV.RIHPELV.....TGSKDHEL.DPRRWKRLETHDVVIECAKISLDPTEASYEDGYSVSHQISARFPHRSADVTTSPYADTQNSYGCATSTPYSTSRLMLLNMPGQLPQTLSSPSTRLITEPPQATLWSPSMVCGMTTPPTSPGNVPPDLSHPYSKVFGTTAGGKGTPLGTPATSPPPAPLCHSDDYVHISLPQATVTPPRKEERMDSARPCLHRQHHLLNDRGSEEPPGSKGSVTLSDLPGFLGDLASEEDSIEKDKEEAAISRELSEITTAEAEPVVPRGGFDSPFYRDSLPGSQRKTHSAASSSQGASVNPEPLHSSLDKLGPDTPKQAFTPIDLPCGSADESPAGDRECQTSLETSIFTPSPCKIPPPTRVGFGSGQPPPYDHLFEVALPKTAHHFVIRKTEELLKKAKGNTEEDGVPSTSPMEVLDRLIQQGADAHSKELNKLPLPSKSVDWTHFGGSPPSDEIRTLRDQLLLLHNQLLYERFKRQQHALRNRRLLRKVIKAAALEEHNAAMKDQLKLQEKDIQMWKVSLQKEQARYNQLQEQRDTMVTKLHSQIRQLQHDREEFYNQSQELQTKLEDCRNMIAELRIELKKANNKVCHTELLLSQVSQKLSNSESVQQQMEFLNRQLLVLGEVNELYLEQLQNKHSDTTKEVEMMKAAYRKELEKNRSHVLQQTQRLDTSQKRILELESHLAKKDHLLLEQKKYLEDVKLQARGQLQAAESRYEAQKRITQVFELEILDLYGRLEKDGLLKKLEEEKAEAAEAAEERLDCCNDGCSDSMVGHNEEASGHNGETKTPRPSSARGSSGSRGGGGSSSSSSELSTPEKPPHQRAGPFSSRWETTMGEASASIPTTVGSLPSSKSFLGMKARELFRNKSESQCDEDGMTSSLSESLKTELGKDLGVEAKIPLNLDGPHPSPPTPDSVGQLHIMDYNETHHEHSGTKLGPEQKLISEEDLNSAVDHHHHHH  
s2:
MNLLPCNPHGNGLLYAGFNQDHGCFACGMENGFRVYNTDPLKEKEKQEFLEGGVGHVEMLFRCNYLALVGGGKKPKYPPNKVMIWDDLKKKTVIEIEFSTEVKAVKLRRDRIVVVLDSMIKVFTFTHNPHQLHVFETCYNPKGLCVLCPNSNNSLLAFPGTHT....GHVQLVDLASTEKPPVDIPAHEGVLSCIALNLQGTRIATAS.EKGTLIRIFDTSSGHLIQELRRGSQAANIYCINFNQDASLICVSSDHGTVHIFAAEDPKRNKQSSLASASFLPKYFSSKWSFSKFQVPSGSPCICAFGTEPNAVIAICADGSYYKFLFNPKGECIRDVYAQFLEMTDDKL...............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................  
s1:
..........................................................................MAQQANVGELLAMLDSPMLGVRDDVTAVFKENLNSDRGPMLVNTLVDYYLETSSQPALHILTTLQEPHDKHLLDRINEYVGKAATRLSILSLLGHVIRLQ.PSWKHKLSQAPLLPSLLKCLKMDTDVVVLTTGVLVLITMLPMIPQSGKQHLLDFFDIFGRLSSWCLKKPGHVAEVYLVHLHASVYALFHRLYGM...YPCNFVSFLRSHYSMKENLETFEEVVKPMMEHV.RIHPELV.....TGSKDHEL.DPRRWKRLETHDVVIECAKISLDPTEASYEDGYSVSHQISARFPHRSADVTTSPYADTQNSYGCATSTPYSTSRLMLLNMPGQLPQTLSSPSTRLITEPPQATLWSPSMVCGMTTPPTSPGNVPPDLSHPYSKVFGTTAGGKGTPLGTPATSPPPAPLCHSDDYVHISLPQATVTPPRKEERMDSARPCLHRQHHLLNDRGSEEPPGSKGSVTLSDLPGFLGDLASEEDSIEKDKEEAAISRELSEITTAEAEPVVPRGGFDSPFYRDSLPGSQRKTHSAASSSQGASVNPEPLHSSLDKLGPDTPKQAFTPIDLPCGSADESPAGDRECQTSLETSIFTPSPCKIPPPTRVGFGSGQPPPYDHLFEVALPKTAHHFVIRKTEELLKKAKGNTEEDGVPSTSPMEVLDRLIQQGADAHSKELNKLPLPSKSVDWTHFGGSPPSDEIRTLRDQLLLLHNQLLYERFKRQQHALRNRRLLRKVIKAAALEEHNAAMKDQLKLQEKDIQMWKVSLQKEQARYNQLQEQRDTMVTKLHSQIRQLQHDREEFYNQSQELQTKLEDCRNMIAELRIELKKANNKVCHTELLLSQVSQKLSNSESVQQQMEFLNRQLLVLGEVNELYLEQLQNKHSDTTKEVEMMKAAYRKELEKNRSHVLQQTQRLDTSQKRILELESHLAKKDHLLLEQKKYLEDVKLQARGQLQAAESRYEAQKRITQVFELEILDLYGRLEKDGLLKKLEEEKAEAAEAAEERLDCCNDGCSDSMVGHNEEASGHNGETKTPRPSSARGSSGSRGGGGSSSSSSELSTPEKPPHQRAGPFSSRWETTMGEASASIPTTVGSLPSSKSFLGMKARELFRNKSESQCDEDGMTSSLSESLKTELGKDLGVEAKIPLNLDGPHPSPPTPDSVGQLHIMDYNETHHEHSGTKLGPEQKLISEEDLNSAVDHHHHHH  
s2:
MNLLPCNPHGNGLLYAGFNQDHGCFACGMENGFRVYNTDPLKEKEKQEFLEGGVGHVEMLFRCNYLALVGGGKKPKYPPNKVMIWDDLKKKTVIEIEFSTEVKAVKLRRDRIVVVLDSMIKVFTFTHNPHQLHVFETCYNPKGLCVLCPNSNNSLLAFPGTHT....GHVQLVDLASTEKPPVDIPAHEGVLSCIALNLQGTRIATAS.EKGTLIRIFDTSSGHLIQELRRGSQAANIYCINFNQDASLICVSSDHGTVHIFAAEDPKRNKQSSLASASFLPKYFSSKWSFSKFQVPSGSPCICAFGTEPNAVIAICADGSYYKFLFNPKGECIRDVYAQFLEMTDDKL...............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................  
s1:
........................MTEDSQRNFRSVYYEKVGFRGVEEKKSLEILLKD.DRLDTEKLCTFSQRF.....PLPSMYRALVWKVL..LGILPPHHESHAKVMMYRKEQYLDVLHALKVVRFVSDATPQAEVYLRMYQLES..GKLPRSP....SFPLEPDDEVFLAIAKAMEEMVEDSVDCYWITRRFVNQLNTKYRDSLPQLPKAFEQYLNLEDGRLLTHLRMCSAAPKLPYDLWFKR.....CFA...GCL....PESSLQRVWDKVVSGSCKILVFVAVEILLTFKIKVMALNSAEKITKFLEN...IPQDSSDAIVSKAIDLWHKHCGTPVHSSDYKDDDDK.  
s2:
MNLLPCNPHGNGLLYAGFNQDHGCFACGMENGFRVYNTDP.....LKEKEKQEFLEGGVGHVEMLFRCNYLALVGGGKKPKYPPNKVMIWDDLKKKTVIEIEFSTEVKAVKLRRDRIVVVLDSMIKVFTFTHNPHQLHVFETCYNPKGLCVLCPNSNNSLLAFPGTHTGHVQLVDLASTEKPPVDIPAHEGVLSCIALNLQGT.RIATASEKGTLIRIFDTSSGHLIQELRRGSQAAN.IYCINFNQDASLICVSSDHGTVHIFAAEDPKRNKQSSLASASFLPKYFSSKWSFSKFQVP....SGSPCICAFGTEPNAVIAICADGSYYKFLFNPKGECIRDVYAQFLEMTDDKL  
s1:
....MHHHHHHGLLYAGFNQDHGCFACGMENGFRVYNTDPLKEKEKQEFLEGGVGHVEMLFRCNYLALVGGGKK......KVMIWDDLKKKTVIEIEFSTEVKAVKLRRDRIVVVLDSMIKVFTFTHNPHQLHVFETCYNPKGLCVLCPNSNNSLLAFPGTHTGHVQLVDLASTEKPPVDIPAHEGVLSCIALNLQGTRIATASEKGTLIRIFDTSSGHLIQELRRGSQAANIYCINFNQDASLICVSSDHGTVHIFAAEDPK..................SKWSFSKFQVPSGSPCICAFGTEPNAVIAICADGSYYKFLFNPKGECIRDVYAQFLEMTDDKL  
s2:
MNLLPCNPHGNGLLYAGFNQDHGCFACGMENGFRVYNTDPLKEKEKQEFLEGGVGHVEMLFRCNYLALVGGGKKPKYPPNKVMIWDDLKKKTVIEIEFSTEVKAVKLRRDRIVVVLDSMIKVFTFTHNPHQLHVFETCYNPKGLCVLCPNSNNSLLAFPGTHTGHVQLVDLASTEKPPVDIPAHEGVLSCIALNLQGTRIATASEKGTLIRIFDTSSGHLIQELRRGSQAANIYCINFNQDASLICVSSDHGTVHIFAAEDPKRNKQSSLASASFLPKYFSSKWSFSKFQVPSGSPCICAFGTEPNAVIAICADGSYYKFLFNPKGECIRDVYAQFLEMTDDKL  
s1:
............................................................................................................................................................................................................................................................................................................................................????????????  
s2:
MNLLPCNPHGNGLLYAGFNQDHGCFACGMENGFRVYNTDPLKEKEKQEFLEGGVGHVEMLFRCNYLALVGGGKKPKYPPNKVMIWDDLKKKTVIEIEFSTEVKAVKLRRDRIVVVLDSMIKVFTFTHNPHQLHVFETCYNPKGLCVLCPNSNNSLLAFPGTHTGHVQLVDLASTEKPPVDIPAHEGVLSCIALNLQGTRIATASEKGTLIRIFDTSSGHLIQELRRGSQAANIYCINFNQDASLICVSSDHGTVHIFAAEDPKRNKQSSLASASFLPKYFSSKWSFSKFQVPSGSPCICAFGTEPNAVIAICADGSYYKFLFNPKGECIRDVYAQFLEMTDDKL  
s1:
............................................................................................................................................................................................................................................................................................................................................????????????  
s2:
MNLLPCNPHGNGLLYAGFNQDHGCFACGMENGFRVYNTDPLKEKEKQEFLEGGVGHVEMLFRCNYLALVGGGKKPKYPPNKVMIWDDLKKKTVIEIEFSTEVKAVKLRRDRIVVVLDSMIKVFTFTHNPHQLHVFETCYNPKGLCVLCPNSNNSLLAFPGTHTGHVQLVDLASTEKPPVDIPAHEGVLSCIALNLQGTRIATASEKGTLIRIFDTSSGHLIQELRRGSQAANIYCINFNQDASLICVSSDHGTVHIFAAEDPKRNKQSSLASASFLPKYFSSKWSFSKFQVPSGSPCICAFGTEPNAVIAICADGSYYKFLFNPKGECIRDVYAQFLEMTDDKL  

> isolde restrain distances "#1.2/F" templateAtoms "#2.6/F" perChain false
> adjustForConfidence true useCoordinateAlignment false kappa 4.40 fallOff
> 2.50 groupName "Reference Distance Restraints"

ISOLDE: Checking and correcting nomenclature for (pseudo)symmetric side
chains...  
[Repeated 1 time(s)]ISOLDE: Corrected atom nomenclature of 44 residues in
model #2.6 to IUPAC-IUB standards.  
Computing secondary structure  
[Repeated 1 time(s)]

> isolde restrain torsions #1.2/F templateResidues #2.6/F adjustForConfidence
> true sidechains true springConstant 250.00 alpha 0.20

ISOLDE: Checking and correcting nomenclature for (pseudo)symmetric side
chains...  
[Repeated 1 time(s)]Computing secondary structure  
[Repeated 1 time(s)]

> hide #!2 models

> select #1

70570 atoms, 71273 bonds, 16 pseudobonds, 4379 residues, 18 models selected  

> isolde sim start #1.2/A-H

ISOLDE: started sim  

> select clear

> isolde sim pause

> matchmaker #2.2 to #1.2

Computing secondary structure  
[Repeated 1 time(s)]  Parameters  
---  
Chain pairing | bb  
Alignment algorithm | Needleman-Wunsch  
Similarity matrix | BLOSUM-62  
SS fraction | 0.3  
Gap open (HH/SS/other) | 18/18/6  
Gap extend | 1  
SS matrix |  |  | H | S | O  
---|---|---|---  
H | 6 | -9 | -6  
S |  | 6 | -6  
O |  |  | 4  
Iteration cutoff | 2  
  
Matchmaker 9ce3, chain B (#1.2) with AlphaFold TSC2_HUMAN chain B, chain B
(#2.2), sequence alignment score = 8146.5  
RMSD between 235 pruned atom pairs is 0.911 angstroms; (across all 1282 pairs:
6.796)  
  

> color #2.2 bychain

> color #2.2 byhetero

> color modify #2.2 hue + 50

ISOLDE: attempting to load PAE matrix for model #2.2 from the AlphaFold-EBI
database. If this fails or you wish to use a different PAE matrix, use the
"Load PAE matrix" button in ISOLDE's reference model restraints widget.  

> alphafold pae #2.2 uniprotId P49815 plot false

Computing secondary structure  
[Repeated 1 time(s)]s1:
MDYKDDDDKAKPTSKDSGLKEKFKILLGLGTPRPNPRSAEGKQTEFIITAEILRELSMECGLNNRIRMIGQICEVAKTKKFEEHAVEALWKAVADLLQPERPLEARHAVLALLKAIVQGQGERLGVLRALFFKVIKDYPSNEDLHERLEVFKALTDNGRHITYLEEELADFVLQWMDVGLSSEFLLVLVNLVKFNSCYLDEYIARMVQMICLLCVRTASSVDIEVSLQVLDAVVCYNCLPAESLPLFIVTLCRTINVKELCEPCWKLMRNLLGTHLGHSAIYNMCHLMEDRAYMEDAPLLRGAVFFVGMALWGAHRLYSLRNSPTSVLPSFYQAMACPNEVVSYEIVLSITRLIKKYRKELQVVAWDILLNIIERLLQQLQTLDSPELRTIVHDLLTTVEELCDQNEFHGSQERYFELVERCADQRPESSLLNLISYRAQSIHPAKDGWIQNLQALMERFFRSESRGAVRIKVLDVLSFVLLINRQFYEEELINSVVISQLSHIPEDKDHQVRKLATQLLVDLAEGCHTHHFNSLLDIIEKVMARSLSPPPELEERDVAAYSASLEDVKTAVLGLLVILQTKLYTLPASHATRVYEMLVSHIQLHYKHSYTLPIASSIRLQAFDFLLLLRADSLHRLGLPNKDGVVRFSPYCVCDYMEPERGSEKKTSGPLSPPTGPPGPAPAGPAVRLGSVPYSLLFRVLLQCLKQESDWKVLKLVLGRLPESLRYKVLIFTSPCSVDQLCSALCSMLSGPKTLERLRGAPEGFSRTDLHLAVVPVLTALISYHNYLDKTKQREMVYCLEQGLIHRCASQCVVALSICSVEMPDIIIKALPVLVVKLTHISATASMAVPLLEFLSTLARLPHLYRNFAAEQYASVFAISLPYTNPSKFNQYIVCLAHHVIAMWFIRCRLPFRKDFVPFITKGLRSNVLLSFDDTPEKDSFRARSTSLNERPKSLRIARPPKQGLNNSPPVKEFKESSAAEAFRCRSISVSEHVVRSRIQTSLTSASLGSADENSVAQADDSLKNLHLELTETCLDMMARYVFSNFTAVPKRSPVGEFLLAGGRTKTWLVGNKLVTVTTSVGTGTRSLLGLDSGELQSGPESSSSPGVHVRQTKEAPAKLESQAGQQVSRGARDRVRSMSGGHGLRVGALDVPASQFLGSATSPGPRTAPAAKPEKASAGTRVPVQEKTNLAAYVPLLTQGWAEILVRRPTGNTSWLMSLENPLSPFSSDINNMPLQELSNALMAAERFKEHRDTALYKSLSVPAASTAKPPPLPRSNT.......................DSAVVMEEGSPGEVPVLVEPPGLEDVEAALGMDRRTDAYSRSSSVSSQEEKSLHAEELVGRGIPIERVVSSEGGRPSVDLSFQPSQPLSKSSSSPELQTLQDILGDPGDKADVGRLSPEVKARSQSGTLDGESAAWSASGEDSRGQPEGPLPSSSPRSPSGLRPRGYTISDSAPSRRGKRVERDALKSRATASNAEKVPGINPSFVFLQLYHSPFFGDESNKPILLPNESQSFERSVQLLDQIPSYDTHKIAVLYVGEGQSNSELAILSNEHGSYRYTEFLTGLGRLIELKDCQPDKVYLGGLDVCGEDGQFTYCWHDDIMQAVFHIATLMPTKDVDKHRCDKKRHLGNDFVSIVYNDSGEDFKLGTIKGQFNFVHVIVTPLDYECNLVSLQCRKDMEGLVDTSVAKIVSDRNLPFVARQMALHANMASQVHHSRSNPTDIYPSKWIARLRHIKRLRQRICEEAAYSNPSLPLVHPPSHSKAPAQTPAEPTPGYEVGQRKRLISSVEDFTEFV  
s2:
........MAKPTSKDSGLKEKFKILLGLGTPRPNPRSAEGKQTEFIITAEILRELSMECGLNNRIRMIGQICEVAKTKKFEEHAVEALWKAVADLLQPERPLEARHAVLALLKAIVQGQGERLGVLRALFFKVIKDYPSNEDLHERLEVFKALTDNGRHITYLEEELADFVLQWMDVGLSSEFLLVLVNLVKFNSCYLDEYIARMVQMICLLCVRTASSVDIEVSLQVLDAVVCYNCLPAESLPLFIVTLCRTINVKELCEPCWKLMRNLLGTHLGHSAIYNMCHLMEDRAYMEDAPLLRGAVFFVGMALWGAHRLYSLRNSPTSVLPSFYQAMACPNEVVSYEIVLSITRLIKKYRKELQVVAWDILLNIIERLLQQLQTLDSPELRTIVHDLLTTVEELCDQNEFHGSQERYFELVERCADQRPESSLLNLISYRAQSIHPAKDGWIQNLQALMERFFRSESRGAVRIKVLDVLSFVLLINRQFYEEELINSVVISQLSHIPEDKDHQVRKLATQLLVDLAEGCHTHHFNSLLDIIEKVMARSLSPPPELEERDVAAYSASLEDVKTAVLGLLVILQTKLYTLPASHATRVYEMLVSHIQLHYKHSYTLPIASSIRLQAFDFLLLLRADSLHRLGLPNKDGVVRFSPYCVCDYMEPERGSEKKTSGPLSPPTGPPGPAPAGPAVRLGSVPYSLLFRVLLQCLKQESDWKVLKLVLGRLPESLRYKVLIFTSPCSVDQLCSALCSMLSGPKTLERLRGAPEGFSRTDLHLAVVPVLTALISYHNYLDKTKQREMVYCLEQGLIHRCASQCVVALSICSVEMPDIIIKALPVLVVKLTHISATASMAVPLLEFLSTLARLPHLYRNFAAEQYASVFAISLPYTNPSKFNQYIVCLAHHVIAMWFIRCRLPFRKDFVPFITKGLRSNVLLSFDDTPEKDSFRARSTSLNERPKSLRIARPPKQGLNNSPPVKEFKESSAAEAFRCRSISVSEHVVRSRIQTSLTSASLGSADENSVAQADDSLKNLHLELTETCLDMMARYVFSNFTAVPKRSPVGEFLLAGGRTKTWLVGNKLVTVTTSVGTGTRSLLGLDSGELQSGPESSSSPGVHVRQTKEAPAKLESQAGQQVSRGARDRVRSMSGGHGLRVGALDVPASQFLGSATSPGPRTAPAAKPEKASAGTRVPVQEKTNLAAYVPLLTQGWAEILVRRPTGNTSWLMSLENPLSPFSSDINNMPLQELSNALMAAERFKEHRDTALYKSLSVPAASTAKPPPLPRSNTVASFSSLYQSSCQGQLHRSVSWADSAVVMEEGSPGEVPVLVEPPGLEDVEAALGMDRRTDAYSRSSSVSSQEEKSLHAEELVGRGIPIERVVSSEGGRPSVDLSFQPSQPLSKSSSSPELQTLQDILGDPGDKADVGRLSPEVKARSQSGTLDGESAAWSASGEDSRGQPEGPLPSSSPRSPSGLRPRGYTISDSAPSRRGKRVERDALKSRATASNAEKVPGINPSFVFLQLYHSPFFGDESNKPILLPNESQSFERSVQLLDQIPSYDTHKIAVLYVGEGQSNSELAILSNEHGSYRYTEFLTGLGRLIELKDCQPDKVYLGGLDVCGEDGQFTYCWHDDIMQAVFHIATLMPTKDVDKHRCDKKRHLGNDFVSIVYNDSGEDFKLGTIKGQFNFVHVIVTPLDYECNLVSLQCRKDMEGLVDTSVAKIVSDRNLPFVARQMALHANMASQVHHSRSNPTDIYPSKWIARLRHIKRLRQRICEEAAYSNPSLPLVHPPSHSKAPAQTPAEPTPGYEVGQRKRLISSVEDFTEFV  
s1:
MDYKDDDDKAKPTSKDSGLKEKFKILLGLGTPRPNPRSAEGKQTEFIITAEILRELSMECGLNNRIRMIGQICEVAKTKKFEEHAVEALWKAVADLLQPERPLEARHAVLALLKAIVQGQGERLGVLRALFFKVIKDYPSNEDLHERLEVFKALTDNGRHITYLEEELADFVLQWMDVGLSSEFLLVLVNLVKFNSCYLDEYIARMVQMICLLCVRTASSVDIEVSLQVLDAVVCYNCLPAESLPLFIVTLCRTINVKELCEPCWKLMRNLLGTHLGHSAIYNMCHLMEDRAYMEDAPLLRGAVFFVGMALWGAHRLYSLRNSPTSVLPSFYQAMACPNEVVSYEIVLSITRLIKKYRKELQVVAWDILLNIIERLLQQLQTLDSPELRTIVHDLLTTVEELCDQNEFHGSQERYFELVERCADQRPESSLLNLISYRAQSIHPAKDGWIQNLQALMERFFRSESRGAVRIKVLDVLSFVLLINRQFYEEELINSVVISQLSHIPEDKDHQVRKLATQLLVDLAEGCHTHHFNSLLDIIEKVMARSLSPPPELEERDVAAYSASLEDVKTAVLGLLVILQTKLYTLPASHATRVYEMLVSHIQLHYKHSYTLPIASSIRLQAFDFLLLLRADSLHRLGLPNKDGVVRFSPYCVCDYMEPERGSEKKTSGPLSPPTGPPGPAPAGPAVRLGSVPYSLLFRVLLQCLKQESDWKVLKLVLGRLPESLRYKVLIFTSPCSVDQLCSALCSMLSGPKTLERLRGAPEGFSRTDLHLAVVPVLTALISYHNYLDKTKQREMVYCLEQGLIHRCASQCVVALSICSVEMPDIIIKALPVLVVKLTHISATASMAVPLLEFLSTLARLPHLYRNFAAEQYASVFAISLPYTNPSKFNQYIVCLAHHVIAMWFIRCRLPFRKDFVPFITKGLRSNVLLSFDDTPEKDSFRARSTSLNERPKSLRIARPPKQGLNNSPPVKEFKESSAAEAFRCRSISVSEHVVRSRIQTSLTSASLGSADENSVAQADDSLKNLHLELTETCLDMMARYVFSNFTAVPKRSPVGEFLLAGGRTKTWLVGNKLVTVTTSVGTGTRSLLGLDSGELQSGPESSSSPGVHVRQTKEAPAKLESQAGQQVSRGARDRVRSMSGGHGLRVGALDVPASQFLGSATSPGPRTAPAAKPEKASAGTRVPVQEKTNLAAYVPLLTQGWAEILVRRPTGNTSWLMSLENPLSPFSSDINNMPLQELSNALMAAERFKEHRDTALYKSLSVPAASTAKPPPLPRSNT.......................DSAVVMEEGSPGEVPVLVEPPGLEDVEAALGMDRRTDAYSRSSSVSSQEEKSLHAEELVGRGIPIERVVSSEGGRPSVDLSFQPSQPLSKSSSSPELQTLQDILGDPGDKADVGRLSPEVKARSQSGTLDGESAAWSASGEDSRGQPEGPLPSSSPRSPSGLRPRGYTISDSAPSRRGKRVERDALKSRATASNAEKVPGINPSFVFLQLYHSPFFGDESNKPILLPNESQSFERSVQLLDQIPSYDTHKIAVLYVGEGQSNSELAILSNEHGSYRYTEFLTGLGRLIELKDCQPDKVYLGGLDVCGEDGQFTYCWHDDIMQAVFHIATLMPTKDVDKHRCDKKRHLGNDFVSIVYNDSGEDFKLGTIKGQFNFVHVIVTPLDYECNLVSLQCRKDMEGLVDTSVAKIVSDRNLPFVARQMALHANMASQVHHSRSNPTDIYPSKWIARLRHIKRLRQRICEEAAYSNPSLPLVHPPSHSKAPAQTPAEPTPGYEVGQRKRLISSVEDFTEFV  
s2:
........MAKPTSKDSGLKEKFKILLGLGTPRPNPRSAEGKQTEFIITAEILRELSMECGLNNRIRMIGQICEVAKTKKFEEHAVEALWKAVADLLQPERPLEARHAVLALLKAIVQGQGERLGVLRALFFKVIKDYPSNEDLHERLEVFKALTDNGRHITYLEEELADFVLQWMDVGLSSEFLLVLVNLVKFNSCYLDEYIARMVQMICLLCVRTASSVDIEVSLQVLDAVVCYNCLPAESLPLFIVTLCRTINVKELCEPCWKLMRNLLGTHLGHSAIYNMCHLMEDRAYMEDAPLLRGAVFFVGMALWGAHRLYSLRNSPTSVLPSFYQAMACPNEVVSYEIVLSITRLIKKYRKELQVVAWDILLNIIERLLQQLQTLDSPELRTIVHDLLTTVEELCDQNEFHGSQERYFELVERCADQRPESSLLNLISYRAQSIHPAKDGWIQNLQALMERFFRSESRGAVRIKVLDVLSFVLLINRQFYEEELINSVVISQLSHIPEDKDHQVRKLATQLLVDLAEGCHTHHFNSLLDIIEKVMARSLSPPPELEERDVAAYSASLEDVKTAVLGLLVILQTKLYTLPASHATRVYEMLVSHIQLHYKHSYTLPIASSIRLQAFDFLLLLRADSLHRLGLPNKDGVVRFSPYCVCDYMEPERGSEKKTSGPLSPPTGPPGPAPAGPAVRLGSVPYSLLFRVLLQCLKQESDWKVLKLVLGRLPESLRYKVLIFTSPCSVDQLCSALCSMLSGPKTLERLRGAPEGFSRTDLHLAVVPVLTALISYHNYLDKTKQREMVYCLEQGLIHRCASQCVVALSICSVEMPDIIIKALPVLVVKLTHISATASMAVPLLEFLSTLARLPHLYRNFAAEQYASVFAISLPYTNPSKFNQYIVCLAHHVIAMWFIRCRLPFRKDFVPFITKGLRSNVLLSFDDTPEKDSFRARSTSLNERPKSLRIARPPKQGLNNSPPVKEFKESSAAEAFRCRSISVSEHVVRSRIQTSLTSASLGSADENSVAQADDSLKNLHLELTETCLDMMARYVFSNFTAVPKRSPVGEFLLAGGRTKTWLVGNKLVTVTTSVGTGTRSLLGLDSGELQSGPESSSSPGVHVRQTKEAPAKLESQAGQQVSRGARDRVRSMSGGHGLRVGALDVPASQFLGSATSPGPRTAPAAKPEKASAGTRVPVQEKTNLAAYVPLLTQGWAEILVRRPTGNTSWLMSLENPLSPFSSDINNMPLQELSNALMAAERFKEHRDTALYKSLSVPAASTAKPPPLPRSNTVASFSSLYQSSCQGQLHRSVSWADSAVVMEEGSPGEVPVLVEPPGLEDVEAALGMDRRTDAYSRSSSVSSQEEKSLHAEELVGRGIPIERVVSSEGGRPSVDLSFQPSQPLSKSSSSPELQTLQDILGDPGDKADVGRLSPEVKARSQSGTLDGESAAWSASGEDSRGQPEGPLPSSSPRSPSGLRPRGYTISDSAPSRRGKRVERDALKSRATASNAEKVPGINPSFVFLQLYHSPFFGDESNKPILLPNESQSFERSVQLLDQIPSYDTHKIAVLYVGEGQSNSELAILSNEHGSYRYTEFLTGLGRLIELKDCQPDKVYLGGLDVCGEDGQFTYCWHDDIMQAVFHIATLMPTKDVDKHRCDKKRHLGNDFVSIVYNDSGEDFKLGTIKGQFNFVHVIVTPLDYECNLVSLQCRKDMEGLVDTSVAKIVSDRNLPFVARQMALHANMASQVHHSRSNPTDIYPSKWIARLRHIKRLRQRICEEAAYSNPSLPLVHPPSHSKAPAQTPAEPTPGYEVGQRKRLISSVEDFTEFV  
s1:
.................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................MAQQANVGELLAMLDSPMLGVRDDVTAVFKENLNSDRGPMLVNTLVDYYLETSSQPALHILTTLQEPHDKHLLDRINEYVGKAATRLSILSLLGHVIRLQPSWKHKLSQAPLLPSLLKCLKMDTDVVVLTTGVLVLITMLPMIPQSGKQHLLDFFDIFGRLSSWCLKKPGHVAEVYLVHLHASVYALFHRLYGMYPCNFVSFLRSHYSMKENLETFEEVVKPMMEHVRIHPELVTGSKDHELDPRRWKRLETHDVVIECAKISLDPTEASYEDGYSVSHQISARFPHRSADVTTSPYADTQNSYGCATSTPYSTSRLMLLNMPGQLPQTLSSPSTRLITEPPQATLWSPSMVCGMTTPPTSPGNVP.PDLSHPYS.....KVFGTTAGGKGTPLGTPATSPPPAPLCHSDDYVHISLPQATVTPPRKEERMDSARPCLHRQHHLLNDRGSEEPPGSKGSV.TLSDLPGFLGDLASEEDSIEKDKEEAAISRELS....EITTAEAEPVVPRGGFDSPFYR.DSLPGSQRKTHSAASSSQ...GASVNPEPLHSSLDKLGPDTPKQAFTPIDLPCGSADESPAGDREC...QTSLETSIFTPSPCKIPPPTRVGFGSGQPPPYDHLFEVALPKTAHHFVIRKTEELLKKAKGNTEEDGVPSTSPMEVLDRLIQQGADAHSKELNK...LPLPSKSVD............WTHFGGSPPSDEIRTLRDQLLLLHNQLLYERFKRQQHALRNRRLLRKVIKAAALEEHNAAMKDQLKLQEKDIQMWKVSLQKEQARYNQLQEQRDTMVTKLHSQIRQLQHDREEFYNQSQELQTKLEDCRNMIAELRIELKKANNKVCHTELLLSQVSQKLSNSESVQQQMEFLNRQLLVLGEVNELYLEQLQNKHSDTTKEVEMMKAAYRKELEKNRSHVLQQTQRLDTSQKRILELESHLAKKDHLLLEQKKYLEDVKLQARGQLQAAESRYEAQKRITQVFELEILDLYGRLEKDGLLKKLEEEKAEAAEAAEERLDCCNDGCSDSMVGHNEEASGHNGETKTPRPSSARGSSGSRGGGGSSSSSSELSTPEKPPHQRAGPFSSRWETTMGEASASIPTTVGSLPSSKSFLGMKARELFRNKSESQCDEDGMTSSLSESLKTELGKDLGVEAKIPLNLDGPHPSPPTPDSVGQLHIMDYNETHHEHSGTKLGPEQKLISEEDLNSAVDHHHHHH  
s2:
MAKPTSKDSGLKEKFKILLGLGTPRPNPRSAEGKQTEFIITAEILRELSMECGLNNRIRMIGQICEVAKTKKFEEHAVEALWKAVADLLQPERPLEARHAVLALLKAIVQGQGERLGVLRALFFKVIKDYPSNEDLHERLEVFKALTDNGRHITYLEEELADFVLQWMDVGLSSEFLLVLVNLVKFNSCYLDEYIARMVQMICLLCVRTASSVDIEVSLQVLDAVVCYNCLPAESLPLFIVTLCRTINVKELCEPCWKLMRNLLGTHLGHSAIYNMCHLMEDRAYMEDAPLLRGAVFFVGMALWGAHRLYSLRNSPTSVLPSFYQAMACPNEVVSYEIVLSITRLIKKYRKELQVVAWDILLNIIERLLQQLQTLDSPELRTIVHDLLTTVEELCDQNEFHGSQERYFELVERCADQRPESSLLNLISYRAQSIHPAKDGWIQNLQALMERFFRSESRGAVRIKVLDVLSFVLLINRQFYEEELINSVVISQLSHIPEDKDHQVRKLATQLLVDLAEGCHTHHFNSLLDIIEKVMARSLSPPPELEERDVAAYSASLEDVKTAVLGLLVILQTKLYTLPASHATRVYEMLVSHIQLHYKHSYTLPIASSIRLQAFDFLLLLRADSLHRLGLPNKDGVVRFSPYCVCDYMEPERGSEKKTSGPLSPPTGPPGPAPAGPAVRLGSVPYSLLFRVLLQCLKQESDWKVLKLVLGRLPESLRYKVLIFTSPCSVDQLCSALCSMLSGPKTLERLRGAPEGFSRTDLHLAVVPVLTALISYHNYLDKTKQREMVYCLEQGLIHRCASQCVVALSICSVEMPDIIIKALPVLVVKLTHISATASMAVPLLEFLSTLARLPHLYRNFAAEQYASVFAISLPYTNPSKFNQYIVCLAHHVIAMWFIRCRLPFRKDFVPFITKGLRSNV..LLSFDDTP....EKDSFRARSTSLNERPKSLRIARPPKQGLN.NSPPVKEFKESSAAEAFRCRSISVSEHVVRSRIQTSLTSA.....SLGSADENSVAQADDSLKNLHLELTETCLDMMARYVFSNFTAVPK.....RSPVGEFLLAGGRTKTWLVGNK.......LVTVTTSVGTGTRSLLGLDSGELQSGPESSSSPGVHVRQTKEA..PAKLESQAGQQVSRGARD.....RVRSMSGGHGLRVG....ALD.VPASQFLG.......SATSP....GPRTAPAAKPEKA.SAGTRVPVQEK....TNLAAYVPLLTQGWAEILVRRPTGNTSWLMSLENPLSPFSSDINNMPLQELSNALMAAERFKEHRDTALYKSLSVPAASTAKPP............PLPRSNTVASFSSLYQSSCQGQLHRSVSWA.DSAVVMEEGSPGEVPVLVEPPG....LEDVEAALGMDRRTDAYSRSSSVSSQEEKSLHAEELVGRG...IPIERVVSSEGGRPSVDLSFQPSQPLSKSSSSPE.LQTLQDILGDPGDKADVGRLSPEVKARSQSGTLDGESAAWSASGEDSRGQPEG...PLPSSSPRSPSGLRPRGYTISDSAPSRRGKRVER...DALKSRATASNAEKVPGINPSFVFLQLYH..SPFFGDESNKPILLPNESQSFERSVQLLDQIPSYDTHKIAVLYVGEGQS.NSELAILSNE..HGSYRYTEFLTGLGRLIE..LKDCQPDKVYLGGLDVCGEDGQFTYCWHDDIMQAVFHIATLMPTKDVDKHRCDKKRHLGNDFVSIVYNDSGE.DFKLGTIKGQFNFVHVIVTPLDYE.CNLVSLQCRKDMEGLVDTSVAKIVS..DRNLPFVARQMALHANMASQVHHSRSNPTDI....YPSKWIARLRHIKRLRQRICEEAAYSNPSLPLVHPPSHSKAPAQTPAEPTPGYEVGQRKRLISSVEDFTEFV............................................................................................................................................................................................................................................  
s1:
.................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................MAQQANVGELLAMLDSPMLGVRDDVTAVFKENLNSDRGPMLVNTLVDYYLETSSQPALHILTTLQEPHDKHLLDRINEYVGKAATRLSILSLLGHVIRLQPSWKHKLSQAPLLPSLLKCLKMDTDVVVLTTGVLVLITMLPMIPQSGKQHLLDFFDIFGRLSSWCLKKPGHVAEVYLVHLHASVYALFHRLYGMYPCNFVSFLRSHYSMKENLETFEEVVKPMMEHVRIHPELVTGSKDHELDPRRWKRLETHDVVIECAKISLDPTEASYEDGYSVSHQISARFPHRSADVTTSPYADTQNSYGCATSTPYSTSRLMLLNMPGQLPQTLSSPSTRLITEPPQATLWSPSMVCGMTTPPTSPGNVP.PDLSHPYS.....KVFGTTAGGKGTPLGTPATSPPPAPLCHSDDYVHISLPQATVTPPRKEERMDSARPCLHRQHHLLNDRGSEEPPGSKGSV.TLSDLPGFLGDLASEEDSIEKDKEEAAISRELS....EITTAEAEPVVPRGGFDSPFYR.DSLPGSQRKTHSAASSSQ...GASVNPEPLHSSLDKLGPDTPKQAFTPIDLPCGSADESPAGDREC...QTSLETSIFTPSPCKIPPPTRVGFGSGQPPPYDHLFEVALPKTAHHFVIRKTEELLKKAKGNTEEDGVPSTSPMEVLDRLIQQGADAHSKELNK.LPLPSKSVDW...THFGGSPPSDEI..........RTLRDQLLLLHNQLLYERFKRQQHALRNRRLLRKVIKAAALEEHNAAMKDQLKLQEKDIQMWKVSLQKEQARYNQLQEQRDTMVTKLHSQIRQLQHDREEFYNQSQELQTKLEDCRNMIAELRIELKKANNKVCHTELLLSQVSQKLSNSESVQQQMEFLNRQLLVLGEVNELYLEQLQNKH...SDTTKEVEMMKAAYRKELEKNRSHVLQQTQRLDTSQKRILELESHLAKKDHLLLEQKKYLEDVKLQARGQLQAAESRYEAQKRITQVFELEILDLYGRLEKDGLLKKLEEEKAEAAEAAEERLDCCNDGCSDSMVGHNEEASGHNGETKTPRPSSARGSSGSRGGGGSSSSSSELSTPEKPPHQRAGPFSSRWETTMGEASASIPTTVGSLPSSKSFLGMKARELFRNKSESQCDEDGMTSSLSESLKTELGKDLGVEAKIPLNLDGPHPSPPTPDSVGQLHIMDYNETHHEHSGTKLGPEQKLISEEDLNSAVDHHHHHH  
s2:
MAKPTSKDSGLKEKFKILLGLGTPRPNPRSAEGKQTEFIITAEILRELSMECGLNNRIRMIGQICEVAKTKKFEEHAVEALWKAVADLLQPERPLEARHAVLALLKAIVQGQGERLGVLRALFFKVIKDYPSNEDLHERLEVFKALTDNGRHITYLEEELADFVLQWMDVGLSSEFLLVLVNLVKFNSCYLDEYIARMVQMICLLCVRTASSVDIEVSLQVLDAVVCYNCLPAESLPLFIVTLCRTINVKELCEPCWKLMRNLLGTHLGHSAIYNMCHLMEDRAYMEDAPLLRGAVFFVGMALWGAHRLYSLRNSPTSVLPSFYQAMACPNEVVSYEIVLSITRLIKKYRKELQVVAWDILLNIIERLLQQLQTLDSPELRTIVHDLLTTVEELCDQNEFHGSQERYFELVERCADQRPESSLLNLISYRAQSIHPAKDGWIQNLQALMERFFRSESRGAVRIKVLDVLSFVLLINRQFYEEELINSVVISQLSHIPEDKDHQVRKLATQLLVDLAEGCHTHHFNSLLDIIEKVMARSLSPPPELEERDVAAYSASLEDVKTAVLGLLVILQTKLYTLPASHATRVYEMLVSHIQLHYKHSYTLPIASSIRLQAFDFLLLLRADSLHRLGLPNKDGVVRFSPYCVCDYMEPERGSEKKTSGPLSPPTGPPGPAPAGPAVRLGSVPYSLLFRVLLQCLKQESDWKVLKLVLGRLPESLRYKVLIFTSPCSVDQLCSALCSMLSGPKTLERLRGAPEGFSRTDLHLAVVPVLTALISYHNYLDKTKQREMVYCLEQGLIHRCASQCVVALSICSVEMPDIIIKALPVLVVKLTHISATASMAVPLLEFLSTLARLPHLYRNFAAEQYASVFAISLPYTNPSKFNQYIVCLAHHVIAMWFIRCRLPFRKDFVPFITKGLRSNV..LLSFDDTP....EKDSFRARSTSLNERPKSLRIARPPKQGLN.NSPPVKEFKESSAAEAFRCRSISVSEHVVRSRIQTSLTSA.....SLGSADENSVAQADDSLKNLHLELTETCLDMMARYVFSNFTAVPK.....RSPVGEFLLAGGRTKTWLVGNK.......LVTVTTSVGTGTRSLLGLDSGELQSGPESSSSPGVHVRQTKEA..PAKLESQAGQQVSRGARDRVRSMSGGHGLRVGALDVPASQFLGSAT.....................SPGPRTAPAAKPEKA.SAGTRVPVQEK....TNLAAYVPLLTQGWAEILVRRPTGNTSWLMSLENPLSPFSSDINNMPLQELSNALMAAERFKEHRDTALYKSLSVPAASTAKPP............PLPRSNTVASFSSLYQSSCQGQLHRSVSWA.DSAVVMEEGSPGEVPVLVEPPG....LEDVEAALGMDRRTDAYSRSSSVSSQEEKSLHAEELVGRG...IPIERVVSSEGGRPSVDLSFQPSQPLSKSSSSPE.LQTLQDILGDPGDKADVGRLSPEVKARSQSGTLDGESAAWSASGEDSRGQPEG...PLPSSSPRSPSGLRPRGYTISDSAPSRRGKRVER...DALKSRATASNAEKVPGINPSFVFLQLYH..SPFFGDESNKPILLPNESQSFERSVQLLDQIPSYDTHKIAVLYVGEGQSNSELAILSNE..HGSYRYTEFLTGLGRLIE..LKDCQPDKVYLGGLDVCGEDGQFTYCWHDDIMQAVFHIATLMPTKDVDKHRCDKKRHLGNDFVSIVYNDSGE.DFKLGTIKGQFNFVHVIVTPLDYE.CNLVSLQCRKDMEGLVDTSVAKIVS..DRNLPFVARQMALHANMASQVHHSRSNPTDIYPSKWIARLRHIKRLRQRICEEAAYSNPSLP.LVHPPSHSKAPAQTPAEPTPGYEVG..QRKRLISSVEDFTEFV................................................................................................................................................................................................................................................  
s1:
...........................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................MTEDSQRNFRSVYYEKVGF....RGVEEKKSLEILLKDDRLDTEKLCTFSQRFPLPSMYRALVWKVLLGILPPHHESHAKVMMYRKEQYLDVLHALKVVRFVSDATPQAEVYLRMYQLES.GKLPRSPSFPLEPDDEVFLAIAKAMEEMVEDSVDCYWITRRFVNQLNTKYRDSLPQLPKAFEQYLNLEDGRLLTHLRMCSAAPKLPYDLWFKRCFAGCLPESSLQRVWDKVVSGSCKILVFVAVEILLTFKIKVMALNSAEKITKFLENIPQDSSDAIVSKAIDLWHKHCGTPVHSSDYKDDDDK  
s2:
MAKPTSKDSGLKEKFKILLGLGTPRPNPRSAEGKQTEFIITAEILRELSMECGLNNRIRMIGQICEVAKTKKFEEHAVEALWKAVADLLQPERPLEARHAVLALLKAIVQGQGERLGVLRALFFKVIKDYPSNEDLHERLEVFKALTDNGRHITYLEEELADFVLQWMDVGLSSEFLLVLVNLVKFNSCYLDEYIARMVQMICLLCVRTASSVDIEVSLQVLDAVVCYNCLPAESLPLFIVTLCRTINVKELCEPCWKLMRNLLGTHLGHSAIYNMCHLMEDRAYMEDAPLLRGAVFFVGMALWGAHRLYSLRNSPTSVLPSFYQAMACPNEVVSYEIVLSITRLIKKYRKELQVVAWDILLNIIERLLQQLQTLDSPELRTIVHDLLTTVEELCDQNEFHGSQERYFELVERCADQRPESSLLNLISYRAQSIHPAKDGWIQNLQALMERFFRSESRGAVRIKVLDVLSFVLLINRQFYEEELINSVVISQLSHIPEDKDHQVRKLATQLLVDLAEGCHTHHFNSLLDIIEKVMARSLSPPPELEERDVAAYSASLEDVKTAVLGLLVILQTKLYTLPASHATRVYEMLVSHIQLHYKHSYTLPIASSIRLQAFDFLLLLRADSLHRLGLPNKDGVVRFSPYCVCDYMEPERGSEKKTSGPLSPPTGPPGPAPAGPAVRLGSVPYSLLFRVLLQCLKQESDWKVLKLVLGRLPESLRYKVLIFTSPCSVDQLCSALCSMLSGPKTLERLRGAPEGFSRTDLHLAVVPVLTALISYHNYLDKTKQREMVYCLEQGLIHRCASQCVVALSICSVEMPDIIIKALPVLVVKLTHISATASMAVPLLEFLSTLARLPHLYRNFAAEQYASVFAISLPYTNPSKFNQYIVCLAHHVIAMWFIRCRLPFRKDFVPFITKGLRSNVLLSFDDTPEKDSFRARSTSLNERPKSLRIARPPKQGLNNSPPVKEFKESSAAEAFRCRSISVSEHVVRSRIQTSLTSASLGSADENSVAQADDSLKNLHLELTETCLDMMARYVFSNFTAVPKRSPVGEFLLAGGRTKTWLVGNKLVTVTTSVGTGTRSLLGLDSGELQSGPESSSSPGVHVRQTKEAPAKLESQAGQQVSRGARDRVRSMSGGHGLRVGALDVPASQFLGSATSPGPRTAPAAKPEKASAGTRVPVQEKTNLAAYVPLLTQGWAEILVRRPTGNTSWLMSLENPLSPFSSDINNMPLQELSNALMAAERFKEHRDTALYKSLSVPAASTAKPPPLPRSNTVASFSSLYQSSCQGQLHRSVSWADSAVVMEEGSPGEVPVLVEPPGLEDVEAALGMDRRTDAYSRSSSVSSQEEKSLHAEELVGRGIPIERVVSSEGGRPSVDLSFQPSQPLSKSSSSPELQTLQDILGDPGDKADVGRLSPEVKARSQSGTLDGESAAWSASGEDSRGQPEGPLPSSSPRSPSGLRPRGYTISDSAPSRRGKRVERDALKSRATASNAEKVPGINPSFVFLQLYHSPFFGDESNKPILLPNESQSFERSVQLLDQIPSYDTHKIAVLYVGEGQSNSELAILSNEHGSYRYTEFLTGLGRLIELKDCQPDKVYLGGLDVCGEDGQFTYCWHDDIMQAVFHIATLMPTKDVDKHRCDKKRHLGNDFVSIVYNDSGEDFKLGTIKGQFNFVHVIVTPLDYECNLVSLQCRKDMEGL.....VDTSVAKIVSDR.NLPFVARQMALHANMASQVHHSRSNP.TDIYPSKWIARLRHIKRLRQRICEEAAYSNPSLPLVHPPSHSKAPAQT..PAEPTPGYEVGQRKRLISSVEDFTEFV.....................................................................................................................................................  
s1:
........................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................MHHHHHHGLLYAGFNQ.DHGCFACGMENGFRVYNT..DPLKEKEKQEFLEGGVGHVEMLFRCNYLALVGGGKKKVMIWDDLKKKTVIEIEFSTEVKAVKLRRDRIVVVLDSMIKVFTFTHNPHQLHVFETCYNPKGLCVLCPNSN....NSLLAFPGTHTGHVQLVDLASTEKPPVDIPAHEGVLSCIALNLQGT........RIATASEKGTLIRIFD.....TSSGHLIQELRRGSQAANIYCINFNQDASLICVSSDHGTVHIFAAEDPKSKWSFSKFQVPSGSPCICAFGTE.PNAVIAICADGSYYKFLFNPK....GECIRDVYAQFLEMTDDKL.....................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................  
s2:
MAKPTSKDSGLKEKFKILLGLGTPRPNPRSAEGKQTEFIITAEILRELSMECGLNNRIRMIGQICEVAKTKKFEEHAVEALWKAVADLLQPERPLEARHAVLALLKAIVQGQGERLGVLRALFFKVIKDYPSNEDLHERLEVFKALTDNGRHITYLEEELADFVLQWMDVGLSSEFLLVLVNLVKFNSCYLDEYIARMVQMICLLCVRTASSVDIEVSLQVLDAVVCYNCLPAESLPLFIVTLCRTINVKELCEPCWKLMRNLLGTHLGHSAIYNMCHLMEDRAYMEDAPLLRGAVFFVGMALWGAHRLYSLRNSPTSVLPSFYQAMACPNEVVSYEIVLSITRLIKKYRKELQVVAWDILLNIIERLLQQLQTLDSPELRTIVHDLLTTVEELCDQNEFHGSQERYFELVERCADQRPESSLLNLISYRAQSIHPAKDGWIQNLQALMERFFRSESRGAVRIKVLDVLSFVLLINRQFYEEELINSVVISQLSHIPEDKDHQVRKLATQLLVDLAEGCHTHHFNSLLDIIEKVMARSLSPPPELEERDVAAYSASLEDVKTAVLGLLVILQTKLYTLPASHATRVYEMLVSHIQLHYKHSYTLPIASSIRLQAFDFLLLLRADSLHRLGLPNKDGVVRFSPYCVCDYMEPERGSEKKTSGPLSPPTGPPGPAPAGPAVRLGSVPYSLLFRVLLQCLKQESDWKVLKLVLGRLPESLRYKVLIFTSPCSVDQLCSALCSMLSGPKTLERLRG.APEGFSRTDLHLAVVPVLTALISYHNYLDKTKQREMVYCLEQGLIH.....RCASQCVVALSICSVEMPDIIIKALPVLVVKLTHISATASMAVPLLEFLSTLARL......PHLYRNFAAEQYASVFAISLPYTNPSKFNQYIVCLAHHVIAMWFIRCRLPFRKDFVPFITKGLRSNVLLSFDDTPEKDSFRARSTSLNERPKSLRIARPPKQGLNNSPPVKEFKESSAAEAFRCRS.......ISVSEHVVRSRIQTSLTSASLGSADENSVAQADDSLKNLHLELTETCLDMMARYVFSNFTAVPKRSPVGEFLLAGGRTKTWLVGNKLVTVTTSVGTGTRSLLGLDSGELQSGPESSSSPGVHVRQTKEAPAKLESQAGQQVSRGARDRVRSMSGGHGLRVGALDVPASQFLGSATSPGPRTAPAAKPEKASAGTRVPVQEKTNLAAYVPLLTQGWAEILVRRPTGNTSWLMSLENPLSPFSSDINNMPLQELSNALMAAERFKEHRDTALYKSLSVPAASTAKPPPLPRSNTVASFSSLYQSSCQGQLHRSVSWADSAVVMEEGSPGEVPVLVEPPGLEDVEAALGMDRRTDAYSRSSSVSSQEEKSLHAEELVGRGIPIERVVSSEGGRPSVDLSFQPSQPLSKSSSSPELQTLQDILGDPGDKADVGRLSPEVKARSQSGTLDGESAAWSASGEDSRGQPEGPLPSSSPRSPSGLRPRGYTISDSAPSRRGKRVERDALKSRATASNAEKVPGINPSFVFLQLYHSPFFGDESNKPILLPNESQSFERSVQLLDQIPSYDTHKIAVLYVGEGQSNSELAILSNEHGSYRYTEFLTGLGRLIELKDCQPDKVYLGGLDVCGEDGQFTYCWHDDIMQAVFHIATLMPTKDVDKHRCDKKRHLGNDFVSIVYNDSGEDFKLGTIKGQFNFVHVIVTPLDYECNLVSLQCRKDMEGLVDTSVAKIVSDRNLPFVARQMALHANMASQVHHSRSNPTDIYPSKWIARLRHIKRLRQRICEEAAYSNPSLPLVHPPSHSKAPAQTPAEPTPGYEVGQRKRLISSVEDFTEFV  
s1:
...................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................????????????  
s2:
MAKPTSKDSGLKEKFKILLGLGTPRPNPRSAEGKQTEFIITAEILRELSMECGLNNRIRMIGQICEVAKTKKFEEHAVEALWKAVADLLQPERPLEARHAVLALLKAIVQGQGERLGVLRALFFKVIKDYPSNEDLHERLEVFKALTDNGRHITYLEEELADFVLQWMDVGLSSEFLLVLVNLVKFNSCYLDEYIARMVQMICLLCVRTASSVDIEVSLQVLDAVVCYNCLPAESLPLFIVTLCRTINVKELCEPCWKLMRNLLGTHLGHSAIYNMCHLMEDRAYMEDAPLLRGAVFFVGMALWGAHRLYSLRNSPTSVLPSFYQAMACPNEVVSYEIVLSITRLIKKYRKELQVVAWDILLNIIERLLQQLQTLDSPELRTIVHDLLTTVEELCDQNEFHGSQERYFELVERCADQRPESSLLNLISYRAQSIHPAKDGWIQNLQALMERFFRSESRGAVRIKVLDVLSFVLLINRQFYEEELINSVVISQLSHIPEDKDHQVRKLATQLLVDLAEGCHTHHFNSLLDIIEKVMARSLSPPPELEERDVAAYSASLEDVKTAVLGLLVILQTKLYTLPASHATRVYEMLVSHIQLHYKHSYTLPIASSIRLQAFDFLLLLRADSLHRLGLPNKDGVVRFSPYCVCDYMEPERGSEKKTSGPLSPPTGPPGPAPAGPAVRLGSVPYSLLFRVLLQCLKQESDWKVLKLVLGRLPESLRYKVLIFTSPCSVDQLCSALCSMLSGPKTLERLRGAPEGFSRTDLHLAVVPVLTALISYHNYLDKTKQREMVYCLEQGLIHRCASQCVVALSICSVEMPDIIIKALPVLVVKLTHISATASMAVPLLEFLSTLARLPHLYRNFAAEQYASVFAISLPYTNPSKFNQYIVCLAHHVIAMWFIRCRLPFRKDFVPFITKGLRSNVLLSFDDTPEKDSFRARSTSLNERPKSLRIARPPKQGLNNSPPVKEFKESSAAEAFRCRSISVSEHVVRSRIQTSLTSASLGSADENSVAQADDSLKNLHLELTETCLDMMARYVFSNFTAVPKRSPVGEFLLAGGRTKTWLVGNKLVTVTTSVGTGTRSLLGLDSGELQSGPESSSSPGVHVRQTKEAPAKLESQAGQQVSRGARDRVRSMSGGHGLRVGALDVPASQFLGSATSPGPRTAPAAKPEKASAGTRVPVQEKTNLAAYVPLLTQGWAEILVRRPTGNTSWLMSLENPLSPFSSDINNMPLQELSNALMAAERFKEHRDTALYKSLSVPAASTAKPPPLPRSNTVASFSSLYQSSCQGQLHRSVSWADSAVVMEEGSPGEVPVLVEPPGLEDVEAALGMDRRTDAYSRSSSVSSQEEKSLHAEELVGRGIPIERVVSSEGGRPSVDLSFQPSQPLSKSSSSPELQTLQDILGDPGDKADVGRLSPEVKARSQSGTLDGESAAWSASGEDSRGQPEGPLPSSSPRSPSGLRPRGYTISDSAPSRRGKRVERDALKSRATASNAEKVPGINPSFVFLQLYHSPFFGDESNKPILLPNESQSFERSVQLLDQIPSYDTHKIAVLYVGEGQSNSELAILSNEHGSYRYTEFLTGLGRLIELKDCQPDKVYLGGLDVCGEDGQFTYCWHDDIMQAVFHIATLMPTKDVDKHRCDKKRHLGNDFVSIVYNDSGEDFKLGTIKGQFNFVHVIVTPLDYECNLVSLQCRKDMEGLVDTSVAKIVSDRNLPFVARQMALHANMASQVHHSRSNPTDIYPSKWIARLRHIKRLRQRICEEAAYSNPSLPLVHPPSHSKAPAQTPAEPTPGYEVGQRKRLISSVEDFTEFV  
s1:
...................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................????????????  
s2:
MAKPTSKDSGLKEKFKILLGLGTPRPNPRSAEGKQTEFIITAEILRELSMECGLNNRIRMIGQICEVAKTKKFEEHAVEALWKAVADLLQPERPLEARHAVLALLKAIVQGQGERLGVLRALFFKVIKDYPSNEDLHERLEVFKALTDNGRHITYLEEELADFVLQWMDVGLSSEFLLVLVNLVKFNSCYLDEYIARMVQMICLLCVRTASSVDIEVSLQVLDAVVCYNCLPAESLPLFIVTLCRTINVKELCEPCWKLMRNLLGTHLGHSAIYNMCHLMEDRAYMEDAPLLRGAVFFVGMALWGAHRLYSLRNSPTSVLPSFYQAMACPNEVVSYEIVLSITRLIKKYRKELQVVAWDILLNIIERLLQQLQTLDSPELRTIVHDLLTTVEELCDQNEFHGSQERYFELVERCADQRPESSLLNLISYRAQSIHPAKDGWIQNLQALMERFFRSESRGAVRIKVLDVLSFVLLINRQFYEEELINSVVISQLSHIPEDKDHQVRKLATQLLVDLAEGCHTHHFNSLLDIIEKVMARSLSPPPELEERDVAAYSASLEDVKTAVLGLLVILQTKLYTLPASHATRVYEMLVSHIQLHYKHSYTLPIASSIRLQAFDFLLLLRADSLHRLGLPNKDGVVRFSPYCVCDYMEPERGSEKKTSGPLSPPTGPPGPAPAGPAVRLGSVPYSLLFRVLLQCLKQESDWKVLKLVLGRLPESLRYKVLIFTSPCSVDQLCSALCSMLSGPKTLERLRGAPEGFSRTDLHLAVVPVLTALISYHNYLDKTKQREMVYCLEQGLIHRCASQCVVALSICSVEMPDIIIKALPVLVVKLTHISATASMAVPLLEFLSTLARLPHLYRNFAAEQYASVFAISLPYTNPSKFNQYIVCLAHHVIAMWFIRCRLPFRKDFVPFITKGLRSNVLLSFDDTPEKDSFRARSTSLNERPKSLRIARPPKQGLNNSPPVKEFKESSAAEAFRCRSISVSEHVVRSRIQTSLTSASLGSADENSVAQADDSLKNLHLELTETCLDMMARYVFSNFTAVPKRSPVGEFLLAGGRTKTWLVGNKLVTVTTSVGTGTRSLLGLDSGELQSGPESSSSPGVHVRQTKEAPAKLESQAGQQVSRGARDRVRSMSGGHGLRVGALDVPASQFLGSATSPGPRTAPAAKPEKASAGTRVPVQEKTNLAAYVPLLTQGWAEILVRRPTGNTSWLMSLENPLSPFSSDINNMPLQELSNALMAAERFKEHRDTALYKSLSVPAASTAKPPPLPRSNTVASFSSLYQSSCQGQLHRSVSWADSAVVMEEGSPGEVPVLVEPPGLEDVEAALGMDRRTDAYSRSSSVSSQEEKSLHAEELVGRGIPIERVVSSEGGRPSVDLSFQPSQPLSKSSSSPELQTLQDILGDPGDKADVGRLSPEVKARSQSGTLDGESAAWSASGEDSRGQPEGPLPSSSPRSPSGLRPRGYTISDSAPSRRGKRVERDALKSRATASNAEKVPGINPSFVFLQLYHSPFFGDESNKPILLPNESQSFERSVQLLDQIPSYDTHKIAVLYVGEGQSNSELAILSNEHGSYRYTEFLTGLGRLIELKDCQPDKVYLGGLDVCGEDGQFTYCWHDDIMQAVFHIATLMPTKDVDKHRCDKKRHLGNDFVSIVYNDSGEDFKLGTIKGQFNFVHVIVTPLDYECNLVSLQCRKDMEGLVDTSVAKIVSDRNLPFVARQMALHANMASQVHHSRSNPTDIYPSKWIARLRHIKRLRQRICEEAAYSNPSLPLVHPPSHSKAPAQTPAEPTPGYEVGQRKRLISSVEDFTEFV  

[Unfortunately have to delete to fit within ticket size limits -- look at ticket history to see full log]

> matchmaker #2/C to #1/C:750-800

Computing secondary structure  
[Repeated 1 time(s)]  Parameters  
---  
Chain pairing | bb  
Alignment algorithm | Needleman-Wunsch  
Similarity matrix | BLOSUM-62  
SS fraction | 0.3  
Gap open (HH/SS/other) | 18/18/6  
Gap extend | 1  
SS matrix |  |  | H | S | O  
---|---|---|---  
H | 6 | -9 | -6  
S |  | 6 | -6  
O |  |  | 4  
Iteration cutoff | 2  
  
Matchmaker 9ce3, chain C (#1.2) with AlphaFold TSC1_HUMAN chain C, chain C
(#2.3), sequence alignment score = 265.1  
RMSD between 36 pruned atom pairs is 0.928 angstroms; (across all 51 pairs:
1.980)  
  

> hide #2.3 models

> isolde sim start #1.2/C:774

ISOLDE: started sim  

> isolde sim stop

Sim termination reason: None  
ISOLDE: Checking and correcting nomenclature for (pseudo)symmetric side
chains...  
ISOLDE: Corrected atom nomenclature of 1 residues in model #1.2 to IUPAC-IUB
standards.  
ISOLDE: stopped sim  

> st

[Repeated 53 time(s)]

> isolde sim start #1.2/C:828

ISOLDE: started sim  

> isolde sim stop

Sim termination reason: None  
ISOLDE: Checking and correcting nomenclature for (pseudo)symmetric side
chains...  
ISOLDE: stopped sim  

> st

[Repeated 23 time(s)]

> isolde sim start #1.2/C:852

ISOLDE: started sim  

> isolde sim stop

Sim termination reason: None  
ISOLDE: Checking and correcting nomenclature for (pseudo)symmetric side
chains...  
ISOLDE: stopped sim  

> isolde sim start #1.2/C:849-855

ISOLDE: started sim  

> isolde sim stop

Sim termination reason: None  
ISOLDE: Checking and correcting nomenclature for (pseudo)symmetric side
chains...  
ISOLDE: stopped sim  

> st

[Repeated 6 time(s)]

> isolde sim start #1.2/C:859

ISOLDE: started sim  

> select clear

> isolde sim stop

Sim termination reason: None  
ISOLDE: Checking and correcting nomenclature for (pseudo)symmetric side
chains...  
ISOLDE: stopped sim  

> st

[Repeated 27 time(s)]

> isolde sim start #1.2/C:887-888

ISOLDE: started sim  

> select clear

> isolde sim stop

Sim termination reason: None  
ISOLDE: Checking and correcting nomenclature for (pseudo)symmetric side
chains...  
ISOLDE: Corrected atom nomenclature of 1 residues in model #1.2 to IUPAC-IUB
standards.  
ISOLDE: stopped sim  

> st

[Repeated 17 time(s)]

> isolde sim start #1.2/C:905

ISOLDE: started sim  

> isolde sim stop

Sim termination reason: None  
ISOLDE: Checking and correcting nomenclature for (pseudo)symmetric side
chains...  
ISOLDE: stopped sim  

> st

[Repeated 54 time(s)]

> isolde sim start #1.2/C:960

ISOLDE: started sim  

> isolde sim stop

Sim termination reason: None  
ISOLDE: Checking and correcting nomenclature for (pseudo)symmetric side
chains...  
ISOLDE: stopped sim  

> st

[Repeated 10 time(s)]

> save working.cxs

Taking snapshot of stepper: 9ce3  

> st

> show #2.4 models

> matchmaker #2/D to #1/D

Computing secondary structure  
[Repeated 1 time(s)]  Parameters  
---  
Chain pairing | bb  
Alignment algorithm | Needleman-Wunsch  
Similarity matrix | BLOSUM-62  
SS fraction | 0.3  
Gap open (HH/SS/other) | 18/18/6  
Gap extend | 1  
SS matrix |  |  | H | S | O  
---|---|---|---  
H | 6 | -9 | -6  
S |  | 6 | -6  
O |  |  | 4  
Iteration cutoff | 2  
  
Matchmaker 9ce3, chain D (#1.2) with AlphaFold TSC1_HUMAN chain D, chain D
(#2.4), sequence alignment score = 5087.2  
RMSD between 37 pruned atom pairs is 0.931 angstroms; (across all 581 pairs:
80.281)  
  

> select ~sel & ##selected

70611 atoms, 71317 bonds, 15 pseudobonds, 4382 residues, 2 models selected  

> matchmaker #2/D to #1/D:1-100

Computing secondary structure  
[Repeated 1 time(s)]  Parameters  
---  
Chain pairing | bb  
Alignment algorithm | Needleman-Wunsch  
Similarity matrix | BLOSUM-62  
SS fraction | 0.3  
Gap open (HH/SS/other) | 18/18/6  
Gap extend | 1  
SS matrix |  |  | H | S | O  
---|---|---|---  
H | 6 | -9 | -6  
S |  | 6 | -6  
O |  |  | 4  
Iteration cutoff | 2  
  
Matchmaker 9ce3, chain D (#1.2) with AlphaFold TSC1_HUMAN chain D, chain D
(#2.4), sequence alignment score = 475  
RMSD between 78 pruned atom pairs is 0.817 angstroms; (across all 95 pairs:
1.601)  
  

> hide #2.4 models

> show #2.4 models

> hide #2.4 models

> isolde sim start #1.2/D:67

ISOLDE: started sim  

> isolde cisflip #1.2/D:67

> isolde sim stop discardTo start

Sim termination reason: None  
reverting to start  
ISOLDE: Checking and correcting nomenclature for (pseudo)symmetric side
chains...  
ISOLDE: stopped sim  

> st

[Repeated 9 time(s)]

> show #2.4 models

> show #2/D

> hide #2.4 models

> select #1/D

9679 atoms, 9756 bonds, 4 pseudobonds, 581 residues, 2 models selected  

> isolde sim start #1.2/D

ISOLDE: started sim  

> select clear

[Repeated 1 time(s)]

> isolde sim pause

> st

[Repeated 81 time(s)]

> isolde sim resume

> isolde sim pause

> st

[Repeated 53 time(s)]

> show #2.4 models

> matchmaker #2/D:100-150 to #1/D

Computing secondary structure  
[Repeated 1 time(s)]  Parameters  
---  
Chain pairing | bb  
Alignment algorithm | Needleman-Wunsch  
Similarity matrix | BLOSUM-62  
SS fraction | 0.3  
Gap open (HH/SS/other) | 18/18/6  
Gap extend | 1  
SS matrix |  |  | H | S | O  
---|---|---|---  
H | 6 | -9 | -6  
S |  | 6 | -6  
O |  |  | 4  
Iteration cutoff | 2  
  
Matchmaker 9ce3, chain D (#1.2) with AlphaFold TSC1_HUMAN chain D, chain D
(#2.4), sequence alignment score = 234.5  
RMSD between 51 pruned atom pairs is 0.622 angstroms; (across all 51 pairs:
0.622)  
  

> color byhetero

> hide #2.4 models

> st

[Repeated 16 time(s)]

> isolde sim resume

> isolde pepflip #1.2/D:170

> isolde sim pause

> st

[Repeated 9 time(s)]

> isolde sim resume

> isolde sim pause

> st

[Repeated 1 time(s)]

> isolde sim resume

> isolde sim pause

> st

[Repeated 16 time(s)]

> isolde sim resume

> isolde sim pause

> st

[Repeated 7 time(s)]

> isolde sim resume

> isolde sim pause

> st

[Repeated 6 time(s)]

> isolde sim resume

> isolde sim pause

> isolde sim resume

> isolde sim pause

> st

[Repeated 33 time(s)]

> isolde sim resume

> isolde sim pause

> st

[Repeated 17 time(s)]

> show #2.4 models

> select #2/D:617-700

665 atoms, 679 bonds, 84 residues, 1 model selected  

> hide #2.4 models

> st

[Repeated 17 time(s)]

> ui mousemode right "mark point"

> marker #5 position 362.2,355.6,158 color yellow radius 1

> label sel text "Seems plausible, but needs confirmation (unstructured in
> monomer)"

> ui mousemode right "isolde tug atom"

> st

[Repeated 1 time(s)]

> show #2.4 models

> hide #2.4 models

> isolde sim resume

> isolde sim pause

> st

> isolde sim resume

> isolde sim pause

> show #2.2 models

> matchmaker #2/B:1-100 to #1/B

Computing secondary structure  
[Repeated 1 time(s)]  Parameters  
---  
Chain pairing | bb  
Alignment algorithm | Needleman-Wunsch  
Similarity matrix | BLOSUM-62  
SS fraction | 0.3  
Gap open (HH/SS/other) | 18/18/6  
Gap extend | 1  
SS matrix |  |  | H | S | O  
---|---|---|---  
H | 6 | -9 | -6  
S |  | 6 | -6  
O |  |  | 4  
Iteration cutoff | 2  
  
Matchmaker 9ce3, chain B (#1.2) with AlphaFold TSC2_HUMAN chain B, chain B
(#2.2), sequence alignment score = 421.9  
RMSD between 57 pruned atom pairs is 0.478 angstroms; (across all 60 pairs:
0.952)  
  

> ui mousemode right "mark point"

> marker #5 position 360.7,308.8,161.3 color yellow radius 1

> label sel text "Plausible but not certain - could be N-terminus of chain B?"

> select clear

> ui mousemode right "isolde tug atom"

> st

[Repeated 25 time(s)]

> show #2.4 models

> select #2/D:690-700

93 atoms, 93 bonds, 11 residues, 1 model selected  

> matchmaker #2/D:690-800 to #1/D

Computing secondary structure  
[Repeated 1 time(s)]  Parameters  
---  
Chain pairing | bb  
Alignment algorithm | Needleman-Wunsch  
Similarity matrix | BLOSUM-62  
SS fraction | 0.3  
Gap open (HH/SS/other) | 18/18/6  
Gap extend | 1  
SS matrix |  |  | H | S | O  
---|---|---|---  
H | 6 | -9 | -6  
S |  | 6 | -6  
O |  |  | 4  
Iteration cutoff | 2  
  
Matchmaker 9ce3, chain D (#1.2) with AlphaFold TSC1_HUMAN chain D, chain D
(#2.4), sequence alignment score = 576.7  
RMSD between 18 pruned atom pairs is 1.069 angstroms; (across all 111 pairs:
7.393)  
  

> hide #2.2 models

> hide #2.4 models

> st

[Repeated 5 time(s)]

> isolde sim resume

> isolde sim pause

> st

[Repeated 17 time(s)]

> select /C,D

70846 atoms, 71771 bonds, 18 pseudobonds, 6369 residues, 9 models selected  

> select clear

> select /C,D

70846 atoms, 71771 bonds, 18 pseudobonds, 6369 residues, 9 models selected  

> select #1/C,D

19841 atoms, 20012 bonds, 6 pseudobonds, 1197 residues, 2 models selected  

> select clear

> ui mousemode right "mark point"

> marker #5 position 363.4,333.1,172 color yellow radius 1

> label sel text "unconvincing sidechain fits... register?"

> ui mousemode right "isolde tug atom"

> select clear

> select #1/D:689-728

735 atoms, 738 bonds, 40 residues, 1 model selected  

> isolde sim resume

> isolde pepflip #1.2/C:273

> isolde pepflip #1.2/C:272

[Repeated 1 time(s)]

> isolde sim pause

> select #1/C:690-710

391 atoms, 393 bonds, 21 residues, 1 model selected  

> label #5:10 text "shifted helix 3 residues towards C-terminus"

> select clear

> isolde sim stop

Sim termination reason: None  
ISOLDE: Checking and correcting nomenclature for (pseudo)symmetric side
chains...  
ISOLDE: Corrected atom nomenclature of 15 residues in model #1.2 to IUPAC-IUB
standards.  
ISOLDE: stopped sim  

> select up

227 atoms, 229 bonds, 14 residues, 2 models selected  

> select up

9885 atoms, 9981 bonds, 612 residues, 2 models selected  

> isolde sim start #1.2/B:41-652

ISOLDE: started sim  

> select clear

[Repeated 1 time(s)]

> isolde pepflip #1.2/B:155

[Repeated 1 time(s)]

> isolde pepflip #1.2/B:158

> isolde sim stop

Sim termination reason: None  
ISOLDE: Checking and correcting nomenclature for (pseudo)symmetric side
chains...  
ISOLDE: Corrected atom nomenclature of 5 residues in model #1.2 to IUPAC-IUB
standards.  
ISOLDE: stopped sim  

> select #1/D:710-2000

4296 atoms, 4315 bonds, 1 pseudobond, 253 residues, 2 models selected  

> isolde sim start #1.2/D:710-969

ISOLDE: started sim  

> select clear

> st

[Repeated 1 time(s)]

> select clear

> st view 12

> st view 15

> st

[Repeated 9 time(s)]

> isolde sim pause

> st

> isolde sim resume

> isolde sim pause

> isolde sim resume

> isolde sim pause

> st

[Repeated 37 time(s)]

> isolde sim resume

> ui mousemode right "mark point"

> marker #5 position 319.9,389.9,266.1 color yellow radius 1

> label sel text "This helix is out of register - should be pseudosymmetric
> with chain C. Try AF-multimer of coiled-coil section"

> select clear

> st #1/D:839

> st

> ui mousemode right "isolde tug atom"

> isolde sim pause

> st

[Repeated 47 time(s)]

> isolde sim resume

> isolde sim pause

> select clear

> st

[Repeated 7 time(s)]

> isolde sim resume

> isolde sim pause

> st

[Repeated 29 time(s)]

> isolde sim resume

> isolde sim pause

> st

[Repeated 5 time(s)]

> isolde sim resume

> isolde sim pause

> isolde sim resume

> select clear

> isolde sim pause

> st

[Repeated 14 time(s)]

> isolde sim resume

> isolde sim pause

> st

[Repeated 8 time(s)]

> isolde sim resume

> isolde sim pause

> st

[Repeated 3 time(s)]

> isolde sim resume

> isolde sim pause

> st

[Repeated 8 time(s)]

> isolde sim stop

Sim termination reason: None  
ISOLDE: Checking and correcting nomenclature for (pseudo)symmetric side
chains...  
ISOLDE: Corrected atom nomenclature of 2 residues in model #1.2 to IUPAC-IUB
standards.  
ISOLDE: stopped sim  

> st

> show #2.5 models

> matchmaker #2.5 to #1.2

Computing secondary structure  
[Repeated 1 time(s)]  Parameters  
---  
Chain pairing | bb  
Alignment algorithm | Needleman-Wunsch  
Similarity matrix | BLOSUM-62  
SS fraction | 0.3  
Gap open (HH/SS/other) | 18/18/6  
Gap extend | 1  
SS matrix |  |  | H | S | O  
---|---|---|---  
H | 6 | -9 | -6  
S |  | 6 | -6  
O |  |  | 4  
Iteration cutoff | 2  
  
Matchmaker 9ce3, chain E (#1.2) with AlphaFold TBCD7_HUMAN chain E, chain E
(#2.5), sequence alignment score = 1492.1  
RMSD between 271 pruned atom pairs is 0.527 angstroms; (across all 276 pairs:
0.764)  
  

> color #2.5 bychain

> color #2.5 byhetero

> color modify #2.5 hue + 50

ISOLDE: attempting to load PAE matrix for model #2.5 from the AlphaFold-EBI
database. If this fails or you wish to use a different PAE matrix, use the
"Load PAE matrix" button in ISOLDE's reference model restraints widget.  

> alphafold pae #2.5 uniprotId Q9P0N9 plot false

Computing secondary structure  
[Repeated 1 time(s)]s1:
MDYKDDDDKAKPTSKDSGLKEKFKILLGLGTPRPNPRSAEGKQTEFIITAEILRELSMECGLNNRIRMIGQICEVAKTKKFEEHAVEALWKAVADLLQP.............ERPLEARHAVLALLKAIVQGQGERLGVLRALFFKVIKDYPSNED..LHERLEVFKALTDNGRHITYLEEELADFVLQWMDVG.LSSEFLLVLVNLVKFNSCYLDEYIARMVQMICLLCVRTASSVDIEVSLQVLDAVVCY.NCLPAESLPLFIVTLCRTINVKELCEPCWKLMRNLLGTHLGHSAIYNMCHLMEDRAYMEDAPLLRGAVFFVGMALWGAHRLYSLRNSPTSVLPSFYQAMACPNEVVSYEIVLSITRLIKKYRKELQVVAWDILLNIIERLLQQLQTLDSPELRTIVHDLLTTVEELCDQNEFHGSQERYFELVERCADQRPESSLLNLISYRAQSIHPAKDGWIQNLQALMERFFRSESRGAVRIKVLDVLSFVLLINRQFYEEELINSVVISQLSHIPEDKDHQVRKLATQLLVDLAEGCHTHHFNSLLDIIEKVMARSLSPPPELEERDVAAYSASLEDVKTAVLGLLVILQTKLYTLPASHATRVYEMLVSHIQLHYKHSYTLPIASSIRLQAFDFLLLLRADSLHRLGLPNKDGVVRFSPYCVCDYMEPERGSEKKTSGPLSPPTGPPGPAPAGPAVRLGSVPYSLLFRVLLQCLKQESDWKVLKLVLGRLPESLRYKVLIFTSPCSVDQLCSALCSMLSGPKTLERLRGAPEGFSRTDLHLAVVPVLTALISYHNYLDKTKQREMVYCLEQGLIHRCASQCVVALSICSVEMPDIIIKALPVLVVKLTHISATASMAVPLLEFLSTLARLPHLYRNFAAEQYASVFAISLPYTNPSKFNQYIVCLAHHVIAMWFIRCRLPFRKDFVPFITKGLRSNVLLSFDDTPEKDSFRARSTSLNERPKSLRIARPPKQGLNNSPPVKEFKESSAAEAFRCRSISVSEHVVRSRIQTSLTSASLGSADENSVAQADDSLKNLHLELTETCLDMMARYVFSNFTAVPKRSPVGEFLLAGGRTKTWLVGNKLVTVTTSVGTGTRSLLGLDSGELQSGPESSSSPGVHVRQTKEAPAKLESQAGQQVSRGARDRVRSMSGGHGLRVGALDVPASQFLGSATSPGPRTAPAAKPEKASAGTRVPVQEKTNLAAYVPLLTQGWAEILVRRPTGNTSWLMSLENPLSPFSSDINNMPLQELSNALMAAERFKEHRDTALYKSLSVPAASTAKPPPLPRSNTDSAVVMEEGSPGEVPVLVEPPGLEDVEAALGMDRRTDAYSRSSSVSSQEEKSLHAEELVGRGIPIERVVSSEGGRPSVDLSFQPSQPLSKSSSSPELQTLQDILGDPGDKADVGRLSPEVKARSQSGTLDGESAAWSASGEDSRGQPEGPLPSSSPRSPSGLRPRGYTISDSAPSRRGKRVERDALKSRATASNAEKVPGINPSFVFLQLYHSPFFGDESNKPILLPNESQSFERSVQLLDQIPSYDTHKIAVLYVGEGQSNSELAILSNEHGSYRYTEFLTGLGRLIELKDCQPDKVYLGGLDVCGEDGQFTYCWHDDIMQAVFHIATLMPTKDVDKHRCDKKRHLGNDFVSIVYNDSGEDFKLGTIKGQFNFVHVIVTPLDYECNLVSLQCRKDMEGLVDTSVAKIVSDRNLPFVARQMALHANMASQVHHSRSNPTDIYPSKWIARLRHIKRLRQRICEEAAYSNPSLPLVHPPSHSKAPAQTPAEPTPGYEVGQRKRLISSVEDFTEFV  
s2:
..............................MTEDSQRNFRSVYYEKVGFRGVEEKKSLEILLKDDRLDTEKLCTFSQRFPLPSMYRALVWKVLLGILPPHHESHAKVMMYRKEQYLDVLHALKVV..RFVSDATPQAEVYLRMYQLESGKLPRSPSFPLEPDDEVFLAIAKAMEEM..VEDSVDCYWITRRFVNQLNTKYRDSLPQLPKAFEQYLNLEDGRLLTHLRMCSAAPKLPYDLWFKR.......CFAGCLPESSLQRVWDKVV.SGSCKILVFVAVEILLTFKIKVMALNSAEKITKFLEN..IPQDS...SDAIVSKAIDLWHKHCGTPVHSS.............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................  
s1:
MDYKDDDDKAKPTSKDSGLKEKFKILLGLGTPRPNPRSAEGKQTEFIITAEILRELSMECGLNNRIRMIGQICEVAKTKKFEEHAVEALWKAVADLLQP.............ERPLEARHAVLALLKAIVQGQGERLGVLRALFFKVIKDYPS.NEDLHERLEVFKALTDNGRHITYLEEELADFVLQWMDVG.LSSEFLLVLVNLVKFNSCYLDEYIARMVQMICLLCVRTASSVDIEVSLQVLDAVVCY.NCLPAESLPLFIVTLCRTINVKELCEPCWKLMRNLLGTHLGHSAIYNMCHLMEDRAYMEDAPLLRGAVFFVGMALWGAHRLYSLRNSPTSVLPSFYQAMACPNEVVSYEIVLSITRLIKKYRKELQVVAWDILLNIIERLLQQLQTLDSPELRTIVHDLLTTVEELCDQNEFHGSQERYFELVERCADQRPESSLLNLISYRAQSIHPAKDGWIQNLQALMERFFRSESRGAVRIKVLDVLSFVLLINRQFYEEELINSVVISQLSHIPEDKDHQVRKLATQLLVDLAEGCHTHHFNSLLDIIEKVMARSLSPPPELEERDVAAYSASLEDVKTAVLGLLVILQTKLYTLPASHATRVYEMLVSHIQLHYKHSYTLPIASSIRLQAFDFLLLLRADSLHRLGLPNKDGVVRFSPYCVCDYMEPERGSEKKTSGPLSPPTGPPGPAPAGPAVRLGSVPYSLLFRVLLQCLKQESDWKVLKLVLGRLPESLRYKVLIFTSPCSVDQLCSALCSMLSGPKTLERLRGAPEGFSRTDLHLAVVPVLTALISYHNYLDKTKQREMVYCLEQGLIHRCASQCVVALSICSVEMPDIIIKALPVLVVKLTHISATASMAVPLLEFLSTLARLPHLYRNFAAEQYASVFAISLPYTNPSKFNQYIVCLAHHVIAMWFIRCRLPFRKDFVPFITKGLRSNVLLSFDDTPEKDSFRARSTSLNERPKSLRIARPPKQGLNNSPPVKEFKESSAAEAFRCRSISVSEHVVRSRIQTSLTSASLGSADENSVAQADDSLKNLHLELTETCLDMMARYVFSNFTAVPKRSPVGEFLLAGGRTKTWLVGNKLVTVTTSVGTGTRSLLGLDSGELQSGPESSSSPGVHVRQTKEAPAKLESQAGQQVSRGARDRVRSMSGGHGLRVGALDVPASQFLGSATSPGPRTAPAAKPEKASAGTRVPVQEKTNLAAYVPLLTQGWAEILVRRPTGNTSWLMSLENPLSPFSSDINNMPLQELSNALMAAERFKEHRDTALYKSLSVPAASTAKPPPLPRSNTDSAVVMEEGSPGEVPVLVEPPGLEDVEAALGMDRRTDAYSRSSSVSSQEEKSLHAEELVGRGIPIERVVSSEGGRPSVDLSFQPSQPLSKSSSSPELQTLQDILGDPGDKADVGRLSPEVKARSQSGTLDGESAAWSASGEDSRGQPEGPLPSSSPRSPSGLRPRGYTISDSAPSRRGKRVERDALKSRATASNAEKVPGINPSFVFLQLYHSPFFGDESNKPILLPNESQSFERSVQLLDQIPSYDTHKIAVLYVGEGQSNSELAILSNEHGSYRYTEFLTGLGRLIELKDCQPDKVYLGGLDVCGEDGQFTYCWHDDIMQAVFHIATLMPTKDVDKHRCDKKRHLGNDFVSIVYNDSGEDFKLGTIKGQFNFVHVIVTPLDYECNLVSLQCRKDMEGLVDTSVAKIVSDRNLPFVARQMALHANMASQVHHSRSNPTDIYPSKWIARLRHIKRLRQRICEEAAYSNPSLPLVHPPSHSKAPAQTPAEPTPGYEVGQRKRLISSVEDFTEFV  
s2:
..............................MTEDSQRNFRSVYYEKVGFRGVEEKKSLEILLKDDRLDTEKLCTFSQRFPLPSMYRALVWKVLLGILPPHHESHAKVMMYRKEQYLDVLHALKV.VRFVSDATPQAEVYLRMYQLESGKLPRSPSFPLEPDDEVFLAIAKAMEEM..VEDSVDCYWITRRFVNQLNTKYRDSLPQLPKAFEQYLNLEDGRLLTHLRMCSAAPKLPYDLWFKR.......CFAGCLPESSLQRVWDKVV.SGSCKILVFVAVEILLTFKIKVMALNSAEKITKFLEN..IPQDS...SDAIVSKAIDLWHKHCGTPVHSS.............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................  
s1:
MAQQANVGELLAMLDSPMLGVRDDVTAVFKENLNSDRGPMLVNTLVDYYLETSSQPALHILTTLQEPHDKHLLDRINEYVGKAATRLSILSLLGHVIRLQPSWKHKLSQAPLLPSLLKCLKMDTDVVVLTTGVLVLITMLPMIPQSGKQHLLDFFDIFGRLSSWCLKKPGHVAEVYLVHLHASVYALFHRLYGMYPCNFVSFLRSHYSMKENLETFEEVVKPMMEHVRIHPELVTGSKDHELDPRRWKRLETHDVVIECAKISLDPTEASYEDGYSVSHQISARFPHRSADVTTSPYADTQNSYGCATSTPYSTSRLMLLNMPGQLPQTLSSPSTRLITEPPQATLWSPSMVCGMTTPPTSPGNVPPDLSHPYSKVFGTTAGGKGTPLGTPATSPPPAPLCHSDDYVHISLPQATVTPPRKEERMDSARPCLHRQHHLLNDRGSEEPPGSKGSVTLSDLPGFLGDLASEEDSIEKDKEEAAISRELSEITTAEAEPVVPRGGFDSPFYRDSLPGSQRKTHSAASSSQGASVNPEPLHSSLDKLGPDTPKQAFTPIDLPCGSADESPAGDRECQTSLETSIFTPSPCKIPPPTRVGFGSGQPPPYDHLFEVALPKTAHHFVIRKTEELLKKAKGNTEED....GVPSTSPMEVL...DRLIQQGADAHSKELNKLPLPS..KSVDW.THFGGSPPSDEIRTLRDQLLLLHNQLLYERFKRQQHALRNRRLLRKVIKAAALEEHNAAMKDQLKLQEKDIQMWKVSLQKEQARYNQLQEQRDTMVTKLHSQIRQLQHDREEFYNQSQ....ELQTKLEDCRNMIAELRIELKKANNKVCHTELLLSQVSQKLSNSESVQQQMEFLNRQLLVLGEVNELYLEQLQNKHSDTTKEVEMMKAAYRKELEKNRSHVLQQTQRLDTSQKRILELESHLAKKDHLLLEQKKYLEDVKLQARGQLQAAESRYEAQKRITQVFELEILDLYGRLEKDGLLKKLEEEKAEAAEAAEERLDCCNDGCSDSMVGHNEEASGHNGETKTPRPSSARGSSGSRGGGGSSSSSSELSTPEKPPHQRAGPFSSRWETTMGEASASIPTTVGSLPSSKSFLGMKARELFRNKSESQCDEDGMTSSLSESLKTELGKDLGVEAKIPLNLDGPHPSPPTPDSVGQLHIMDYNETHHEHSGTKLGPEQKLISEEDLNSAVDHHHHHH  
s2:
..............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................MTEDSQRNFRSVYYEKVGFRGVEEKKSLEILLKDDRLDTEKLCTFSQRF...PLPSMYRALVWKVLLGILPPH..........HESHAKVMMYRKEQYLDVLHALKVVRFV.............SDATPQAEVYLRMYQLESGKLPRSPSFPLEPDDEVFLAIAKAMEEMVEDSVDCYWITRRFVNQLNTKYRDSLPQLPKAFEQYLNLEDGRLLTHLRMCSAAPKL......PYDLWFKR...CFAGCLPESSLQRVWDKVVSGSCKILVFVAVEILLTFKIKVMALNSAEKITKFLENIPQDSSDAIVSKAIDLWHKHCGTPVHSS...............................................................................................................................................................................................................................................................  
s1:
MAQQANVGELLAMLDSPMLGVRDDVTAVFKENLNSDRGPMLVNTLVDYYLETSSQPALHILTTLQEPHDKHLLDRINEYVGKAATRLSILSLLGHVIRLQPSWKHKLSQAPLLPSLLKCLKMDTDVVVLTTGVLVLITMLPMIPQSGKQHLLDFFDIFGRLSSWCLKKPGHVAEVYLVHLHASVYALFHRLYGMYPCNFVSFLRSHYSMKENLETFEEVVKPMMEHVRIHPELVTGSKDHELDPRRWKRLETHDVVIECAKISLDPTEASYEDGYSVSHQISARFPHRSADVTTSPYADTQNSYGCATSTPYSTSRLMLLNMPGQLPQTLSSPSTRLITEPPQATLWSPSMVCGMTTPPTSPGNVPPDLSHPYSKVFGTTAGGKGTPLGTPATSPPPAPLCHSDDYVHISLPQATVTPPRKEERMDSARPCLHRQHHLLNDRGSEEPPGSKGSVTLSDLPGFLGDLASEEDSIEKDKEEAAISRELSEITTAEAEPVVPRGGFDSPFYRDSLPGSQRKTHSAASSSQGASVNPEPLHSSLDKLGPDTPKQAFTPIDLPCGSADESPAGDRECQTSLETSIFTPSPCKIPPPTRVGFGSGQPPPYDHLFEVALPKTAHHFVIRKTEELLKKAKGNTEEDGVPSTSPMEVLDRLIQQGADAHSKELNKLPLPSKSVDWTHFGGSPPSDEIRTLRDQLLLLHNQLLYERFKRQQHALRNRRLLRKVIKAAALEEHNAAMKDQLKLQEKDIQMWKVSLQKEQARYNQLQEQRDTMVTKLHSQIRQLQHDREEFYNQSQELQTKLEDCRNMIAELRIELKKANNKVCHTELLLSQV...SQKLSNSESVQQQMEFLNRQLLVLGEVNELYLEQLQNKHSDTTKEVEMMKAAYRKELEKNRSHVLQQTQRLDTSQKRILELESHLAKKDHLLLEQKKYLEDVKLQARGQLQAAESRYEAQKRITQVFELEILDLYG....RLEK.DGLLKKLEEEKAEAAEA.AEERLDCCNDGCSDSMVGHNEEASGHNGETKTPRPSSARGSSGSRGGGGSSSSSSELSTPEKPPHQRAGPFSSRWETTMGEASASIPTTVGSLPSSKSFLGMKARELFRNKSESQCDEDGMTSSLSESLKTELGKDLGVEAKIPLNLDGPHPSPPTPDSVGQLHIMDYNETHHEHSGTKLGPEQKLISEEDLNSAVDHHHHHH  
s2:
.......................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................MTEDSQRNFRSVYYEK.VGFRGVEEKKSLEILLKDDRLDTEKLCTFSQRF.PLPSMYRALVWKVLLGILP.....PHHESHAKVMMYRKEQYLDVLHALKV.VRFVSDATPQAEVYLRMYQLESGKLPRSPSFP..LEPDDEVFLAIAKAMEEMVEDSVDCYWITRRFVNQLNTKYRDSLPQLPKAFEQYLNLEDGRLLTHLRMCSAAPKLPYDLWFKRCFAG..CLPESSLQRVWDKVVSGSCKILVFVAVEILLTFKIKVMALNSAEKITKFLENIPQDSSDAIVSKAIDLWHKHCGTPV..HSS......................................................................................................................................................................................  
s1:
MTEDSQRNFRSVYYEKVGFRGVEEKKSLEILLKDDRLDTEKLCTFSQRFPLPSMYRALVWKVLLGILPPHHESHAKVMMYRKEQYLDVLHALKVVRFVSDATPQAEVYLRMYQLESGKLPRSPSFPLEPDDEVFLAIAKAMEEMVEDSVDCYWITRRFVNQLNTKYRDSLPQLPKAFEQYLNLEDGRLLTHLRMCSAAPKLPYDLWFKRCFAGCLPESSLQRVWDKVVSGSCKILVFVAVEILLTFKIKVMALNSAEKITKFLENIPQDSSDAIVSKAIDLWHKHCGTPVHSSDYKDDDDK  
s2:
MTEDSQRNFRSVYYEKVGFRGVEEKKSLEILLKDDRLDTEKLCTFSQRFPLPSMYRALVWKVLLGILPPHHESHAKVMMYRKEQYLDVLHALKVVRFVSDATPQAEVYLRMYQLESGKLPRSPSFPLEPDDEVFLAIAKAMEEMVEDSVDCYWITRRFVNQLNTKYRDSLPQLPKAFEQYLNLEDGRLLTHLRMCSAAPKLPYDLWFKRCFAGCLPESSLQRVWDKVVSGSCKILVFVAVEILLTFKIKVMALNSAEKITKFLENIPQDSSDAIVSKAIDLWHKHCGTPVHSS........  
s1:
MHHHHHHGLLYAGFNQDHGCFACGMENGFRVYNTDP.....LKEKEKQEFLEGGVGHVEMLFRCNYLALVG.GGKKKVMIWDDLKKKTVIEIEFSTEVKAVKLRRDRIVVVLDSMIKVFTFTHNPHQLHVFETCYNPKGLCVLCPNSNNSLLAFPGTHTGHVQLVDLASTEKPPVDIPAHEGVLSCIALNLQGT.RIATASEKGTLIRIFDTSSGHLIQELRRGSQAANI.YCINFNQDASLICVSSDHGTVHIFAAEDPKSKWSFSKFQVPSGSPCICAFG......TEPNAVIAICADGSYYKFLFNPKGECIRDVYAQFLEMTDDKL.......  
s2:
....................MTEDSQRNFRSVYYEKVGFRGVEEKKSLEILLKD.DRLDTEKLCTFSQRFPLPSMYRALVWKVLLG..ILPPHHESHAKVMMYRKEQYLDVLHALKVVRFVSDATPQAEVYLRMYQLES..GKLPRSP....SFPLEPDDEVFLAIAKAMEEMVEDSVDCYWITRRFVNQLNTKYRDSLPQLPKAFEQYLNLEDGRLLTHLRMCSAAPKLPYDLWFKR.....C..........FAGCLPESSLQRVWDKVVSGSCKILVFVAVEILLTFKIKVMALNSAEKITKFLENIPQDSSDAIVSKAIDLWHKHCGTPVHSS  
s1:
.........................................................................................................................................................................................................................................................................................????????????  
s2:
MTEDSQRNFRSVYYEKVGFRGVEEKKSLEILLKDDRLDTEKLCTFSQRFPLPSMYRALVWKVLLGILPPHHESHAKVMMYRKEQYLDVLHALKVVRFVSDATPQAEVYLRMYQLESGKLPRSPSFPLEPDDEVFLAIAKAMEEMVEDSVDCYWITRRFVNQLNTKYRDSLPQLPKAFEQYLNLEDGRLLTHLRMCSAAPKLPYDLWFKRCFAGCLPESSLQRVWDKVVSGSCKILVFVAVEILLTFKIKVMALNSAEKITKFLENIPQDSSDAIVSKAIDLWHKHCGTPVHSS  
s1:
.........................................................................................................................................................................................................................................................................................????????????  
s2:
MTEDSQRNFRSVYYEKVGFRGVEEKKSLEILLKDDRLDTEKLCTFSQRFPLPSMYRALVWKVLLGILPPHHESHAKVMMYRKEQYLDVLHALKVVRFVSDATPQAEVYLRMYQLESGKLPRSPSFPLEPDDEVFLAIAKAMEEMVEDSVDCYWITRRFVNQLNTKYRDSLPQLPKAFEQYLNLEDGRLLTHLRMCSAAPKLPYDLWFKRCFAGCLPESSLQRVWDKVVSGSCKILVFVAVEILLTFKIKVMALNSAEKITKFLENIPQDSSDAIVSKAIDLWHKHCGTPVHSS  

> isolde restrain distances "#1.2/E" templateAtoms "#2.5/E" perChain false
> adjustForConfidence true useCoordinateAlignment false kappa 4.40 fallOff
> 2.50 groupName "Reference Distance Restraints"

ISOLDE: Checking and correcting nomenclature for (pseudo)symmetric side
chains...  
[Repeated 1 time(s)]ISOLDE: Corrected atom nomenclature of 47 residues in
model #2.5 to IUPAC-IUB standards.  
Computing secondary structure  
[Repeated 1 time(s)]

> isolde restrain torsions #1.2/E templateResidues #2.5/E adjustForConfidence
> true sidechains true springConstant 250.00 alpha 0.20

ISOLDE: Checking and correcting nomenclature for (pseudo)symmetric side
chains...  
[Repeated 1 time(s)]Computing secondary structure  
[Repeated 1 time(s)]

> select #1/E

4514 atoms, 4569 bonds, 276 residues, 1 model selected  

> hide #2.5 models

> isolde sim start #1.2/E

ISOLDE: started sim  

> select clear

> isolde sim pause

> select up

24 atoms, 23 bonds, 1 residue, 1 model selected  

> ra

> isolde sim resume

> st

[Repeated 1 time(s)]

> select up

7 atoms, 6 bonds, 1 residue, 1 model selected  

> ra

> st

[Repeated 24 time(s)]

> isolde sim pause

> st

[Repeated 1 time(s)]

> select up

11 atoms, 10 bonds, 1 residue, 2 models selected  

> ra

> isolde sim resume

> isolde sim pause

> select up

11 atoms, 10 bonds, 1 residue, 1 model selected  

> ra

> isolde sim resume

> isolde sim pause

> st

[Repeated 23 time(s)]

> ra

> isolde sim resume

> isolde sim pause

> isolde sim resume

> isolde sim pause

> isolde sim stop

Sim termination reason: None  
ISOLDE: Checking and correcting nomenclature for (pseudo)symmetric side
chains...  
ISOLDE: Corrected atom nomenclature of 1 residues in model #1.2 to IUPAC-IUB
standards.  
ISOLDE: stopped sim  

> ht ND

Set protonation of HIS #1.2/E:71 to ND  

> select #1/E

4514 atoms, 4569 bonds, 276 residues, 1 model selected  

> isolde sim start #1.2/E

ISOLDE: started sim  

> select clear

> isolde sim pause

> select clear

> st

> select #1/E

4514 atoms, 4569 bonds, 276 residues, 1 model selected  

> rd

> isolde sim resume

> select clear

> isolde sim pause

> st

[Repeated 19 time(s)]

> select up

20 atoms, 20 bonds, 1 residue, 1 model selected  

> rt

> isolde sim resume

> select clear

> st

[Repeated 4 time(s)]

> ra

> select clear

> isolde sim pause

> st

[Repeated 7 time(s)]

> isolde sim resume

> isolde sim pause

> st

[Repeated 16 time(s)]

> isolde sim resume

> isolde sim pause

> st

[Repeated 13 time(s)]

> isolde sim resume

> isolde sim pause

> st

[Repeated 20 time(s)]

> rt

> isolde sim resume

> isolde sim pause

> st

[Repeated 86 time(s)]

> isolde sim resume

> isolde sim pause

> st

[Repeated 21 time(s)]

> isolde sim resume

> isolde sim pause

> st

[Repeated 24 time(s)]

> isolde sim stop

Sim termination reason: None  
ISOLDE: Checking and correcting nomenclature for (pseudo)symmetric side
chains...  
ISOLDE: Corrected atom nomenclature of 3 residues in model #1.2 to IUPAC-IUB
standards.  
ISOLDE: stopped sim  

> st

[Repeated 2 time(s)]

> show #2.6 models

> matchmaker #2.6 to #1.2

Computing secondary structure  
[Repeated 1 time(s)]  Parameters  
---  
Chain pairing | bb  
Alignment algorithm | Needleman-Wunsch  
Similarity matrix | BLOSUM-62  
SS fraction | 0.3  
Gap open (HH/SS/other) | 18/18/6  
Gap extend | 1  
SS matrix |  |  | H | S | O  
---|---|---|---  
H | 6 | -9 | -6  
S |  | 6 | -6  
O |  |  | 4  
Iteration cutoff | 2  
  
Matchmaker 9ce3, chain F (#1.2) with AlphaFold WIPI3_HUMAN chain F, chain F
(#2.6), sequence alignment score = 1533.7  
RMSD between 287 pruned atom pairs is 0.651 angstroms; (across all 305 pairs:
1.514)  
  

> color #2.6 bychain

> color #2.6 byhetero

> color modify #2.6 hue + 50

ISOLDE: attempting to load PAE matrix for model #2.6 from the AlphaFold-EBI
database. If this fails or you wish to use a different PAE matrix, use the
"Load PAE matrix" button in ISOLDE's reference model restraints widget.  

> alphafold pae #2.6 uniprotId Q5MNZ6 plot false

Computing secondary structure  
[Repeated 1 time(s)]s1:
MDYKDDDDKAKPTSKDSGLKEKFKILLGLGTPRPNPRSAEGKQTEFIITAEILRELSMECGLNNRIRMIGQICEVAKTKKFEEHAVEALWKAVADLLQPERPLEARHAVLALLKAIVQGQGERLGVLRALFFKVIKDYPSNEDLHERLEVFKALTDNGRHITYLEEELADFVLQWMDVGLSSEFLLVLVNLVKFNSCYLDEYIARMVQMICLLCVRTASSVDIEVSLQVLDAVVCYNCLPAESLPLFIVTLCRTINVKELCEPCWKLMRNLLGTHLGHSAIYNMCHLMED.RAYMEDAPLLRGAVFFVGMALWGAHRLYSLRNSPTSVLPSFYQAMACPNEVVSYEIVLSITRLIKKYRKELQ..VVAWDILLNIIERLLQQLQTLDSPELRTIVHDLLTTVEELCD....QNE....FHGSQERYFELVERCADQRP...ESSLLNLISYRAQSIHPAKDGWIQNLQALMERFFRSESRGAVRIKVLDVLSFVLLINRQFYEEELINSVVISQLSHIPEDKDHQVRKLATQLLVDLAEGCHTHHFNSLLDIIEKVMARSLSP........PPEL......EERDVAAYSASLEDVKTAVLGLLVILQTKLYTLPASHATRVYEMLVSHIQLHYKHSYTLPIASSIRLQAFDFLLLLRADSLHRLGLPNKDGVVRFSPYCVCDYMEPERGSEKKTSGPLSPPTGPPGPAPAGPAVRLGSVPYSLLFRVLLQCLKQESDWKVLKLVLGRLPESLRYKVLIFTSPCSVDQLCSALCSMLSGPKTLERLRGAPEGFSRTDLHLAVVPVLTALISYHNYLDKTKQREMVYCLEQGLIHRCASQCVVALSICSVEMPDIIIKALPVLVVKLTHISATASMAVPLLEFLSTLARLPHLYRNFAAEQYASVFAISLPYTNPSKFNQYIVCLAHHVIAMWFIRCRLPFRKDFVPFITKGLRSNVLLSFDDTPEKDSFRARSTSLNERPKSLRIARPPKQGLNNSPPVKEFKESSAAEAFRCRSISVSEHVVRSRIQTSLTSASLGSADENSVAQADDSLKNLHLELTETCLDMMARYVFSNFTAVPKRSPVGEFLLAGGRTKTWLVGNKLVTVTTSVGTGTRSLLGLDSGELQSGPESSSSPGVHVRQTKEAPAKLESQAGQQVSRGARDRVRSMSGGHGLRVGALDVPASQFLGSATSPGPRTAPAAKPEKASAGTRVPVQEKTNLAAYVPLLTQGWAEILVRRPTGNTSWLMSLENPLSPFSSDINNMPLQELSNALMAAERFKEHRDTALYKSLSVPAASTAKPPPLPRSNTDSAVVMEEGSPGEVPVLVEPPGLEDVEAALGMDRRTDAYSRSSSVSSQEEKSLHAEELVGRGIPIERVVSSEGGRPSVDLSFQPSQPLSKSSSSPELQTLQDILGDPGDKADVGRLSPEVKARSQSGTLDGESAAWSASGEDSRGQPEGPLPSSSPRSPSGLRPRGYTISDSAPSRRGKRVERDALKSRATASNAEKVPGINPSFVFLQLYHSPFFGDESNKPILLPNESQSFERSVQLLDQIPSYDTHKIAVLYVGEGQSNSELAILSNEHGSYRYTEFLTGLGRLIELKDCQPDKVYLGGLDVCGEDGQFTYCWHDDIMQAVFHIATLMPTKDVDKHRCDKKRHLGNDFVSIVYNDSGEDFKLGTIKGQFNFVHVIVTPLDYECNLVSLQCRKDMEGLVDTSVAKIVSDRNLPFVARQMALHANMASQVHHSRSNPTDIYPSKWIARLRHIKRLRQRICEEAAYSNPSLPLVHPPSHSKAPAQTPAEPTPGYEVGQRKRLISSVEDFTEFV  
s2:
.................................................................................................................................................................................................................................................................MNLL.PCNPHGNGLLYAGFNQDHGCFACGMENGFRVYNTDPLKEKEKQEFLEGGVGHVEMLF..RCNYLALVGGGKKPKYPPNKVMIWDDLKKKTVIEIEFSTEVKAVKLRRDRIVVVLDSMIKVFTFTHNPH.QLHVFETCYNPKGLCVLCPNSNNSLLAFPGTHTGHVQLVDLASTEKPPVDIPAHEGVLSCIALNLQGTRIATASEKGTLIRIFDTSSGHLIQELRRGSQAANIYCINFN.QDASLICVSSDHGTVHIFAAEDPKRNKQSS.....LASASFLPKYFSSKWSFSKFQVPSGSPCICAFGTEPNAVIAICADGSYYKFLFNPKGECIRDVYAQFLEMTDDKL.........................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................  
s1:
MDYKDDDDKAKPTSKDSGLKEKFKILLGLGTPRPNPRSAEGKQTEFIITAEILRELSMECGLNNRIRMIGQICEVAKTKKFEEHAVEALWKAVADLLQPERPLEARHAVLALLKAIVQGQGERLGVLRALFFKVIKDYPSNEDLHERLEVFKALTDNGRHITYLEEELADFVLQWMDVGLSSEFLLVLVNLVKFNSCYLDEYIARMVQMICLLCVRTASSVDIEVSLQVLDAVVCYNCLPAESLPLFIVTLCRTINVKELCEPCWKLMRNLLGTHLGHSAIYNMCHLMED.RAYMEDAPLLRGAVFFVGMALWGAHRLYSLRNSPTSVLPSFYQAMACPNEVVSYEIVLSITRLIKKYRKELQ..VVAWDILLNIIERLLQQLQTLDSPELRTIVHDLLTTVEELCD....QNE....FHGSQERYFELVERCADQRP...ESSLLNLISYRAQSIHPAKDGWIQNLQALMERFFRSESRGAVRIKVLDVLSFVLLINRQFYEEELINSVVISQLSHIPEDKDHQVRKLATQLLVDLAEGCHTHHFNSLLDIIEKVMARSLSP........PPEL......EERDVAAYSASLEDVKTAVLGLLVILQTKLYTLPASHATRVYEMLVSHIQLHYKHSYTLPIASSIRLQAFDFLLLLRADSLHRLGLPNKDGVVRFSPYCVCDYMEPERGSEKKTSGPLSPPTGPPGPAPAGPAVRLGSVPYSLLFRVLLQCLKQESDWKVLKLVLGRLPESLRYKVLIFTSPCSVDQLCSALCSMLSGPKTLERLRGAPEGFSRTDLHLAVVPVLTALISYHNYLDKTKQREMVYCLEQGLIHRCASQCVVALSICSVEMPDIIIKALPVLVVKLTHISATASMAVPLLEFLSTLARLPHLYRNFAAEQYASVFAISLPYTNPSKFNQYIVCLAHHVIAMWFIRCRLPFRKDFVPFITKGLRSNVLLSFDDTPEKDSFRARSTSLNERPKSLRIARPPKQGLNNSPPVKEFKESSAAEAFRCRSISVSEHVVRSRIQTSLTSASLGSADENSVAQADDSLKNLHLELTETCLDMMARYVFSNFTAVPKRSPVGEFLLAGGRTKTWLVGNKLVTVTTSVGTGTRSLLGLDSGELQSGPESSSSPGVHVRQTKEAPAKLESQAGQQVSRGARDRVRSMSGGHGLRVGALDVPASQFLGSATSPGPRTAPAAKPEKASAGTRVPVQEKTNLAAYVPLLTQGWAEILVRRPTGNTSWLMSLENPLSPFSSDINNMPLQELSNALMAAERFKEHRDTALYKSLSVPAASTAKPPPLPRSNTDSAVVMEEGSPGEVPVLVEPPGLEDVEAALGMDRRTDAYSRSSSVSSQEEKSLHAEELVGRGIPIERVVSSEGGRPSVDLSFQPSQPLSKSSSSPELQTLQDILGDPGDKADVGRLSPEVKARSQSGTLDGESAAWSASGEDSRGQPEGPLPSSSPRSPSGLRPRGYTISDSAPSRRGKRVERDALKSRATASNAEKVPGINPSFVFLQLYHSPFFGDESNKPILLPNESQSFERSVQLLDQIPSYDTHKIAVLYVGEGQSNSELAILSNEHGSYRYTEFLTGLGRLIELKDCQPDKVYLGGLDVCGEDGQFTYCWHDDIMQAVFHIATLMPTKDVDKHRCDKKRHLGNDFVSIVYNDSGEDFKLGTIKGQFNFVHVIVTPLDYECNLVSLQCRKDMEGLVDTSVAKIVSDRNLPFVARQMALHANMASQVHHSRSNPTDIYPSKWIARLRHIKRLRQRICEEAAYSNPSLPLVHPPSHSKAPAQTPAEPTPGYEVGQRKRLISSVEDFTEFV  
s2:
.................................................................................................................................................................................................................................................................MNLL.PCNPHGNGLLYAGFNQDHGCFACGMENGFRVYNTDPLKEKEKQEFLEGGVGHVEMLF..RCNYLALVGGGKKPKYPPNKVMIWDDLKKKTVIEIEFSTEVKAVKLRRDRIVVVLDSMIKVFTFTHNPH.QLHVFETCYNPKGLCVLCPNSNNSLLAFPGTHTGHVQLVDLASTEKPPVDIPAHEGVLSCIALNLQGTRIATASEKGTLIRIFDTSSGHLIQELRRGSQAANIYCINFN.QDASLICVSSDHGTVHIFAAEDPKRNKQSS.....LASASFLPKYFSSKWSFSKFQVPSGSPCICAFGTEPNAVIAICADGSYYKFLFNPKGECIRDVYAQFLEMTDDKL.........................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................  
s1:
..........................................................................MAQQANVGELLAMLDSPMLGVRDDVTAVFKENLNSDRGPMLVNTLVDYYLETSSQPALHILTTLQEPHDKHLLDRINEYVGKAATRLSILSLLGHVIRLQ.PSWKHKLSQAPLLPSLLKCLKMDTDVVVLTTGVLVLITMLPMIPQSGKQHLLDFFDIFGRLSSWCLKKPGHVAEVYLVHLHASVYALFHRLYGM...YPCNFVSFLRSHYSMKENLETFEEVVKPMMEHV.RIHPELV.....TGSKDHEL.DPRRWKRLETHDVVIECAKISLDPTEASYEDGYSVSHQISARFPHRSADVTTSPYADTQNSYGCATSTPYSTSRLMLLNMPGQLPQTLSSPSTRLITEPPQATLWSPSMVCGMTTPPTSPGNVPPDLSHPYSKVFGTTAGGKGTPLGTPATSPPPAPLCHSDDYVHISLPQATVTPPRKEERMDSARPCLHRQHHLLNDRGSEEPPGSKGSVTLSDLPGFLGDLASEEDSIEKDKEEAAISRELSEITTAEAEPVVPRGGFDSPFYRDSLPGSQRKTHSAASSSQGASVNPEPLHSSLDKLGPDTPKQAFTPIDLPCGSADESPAGDRECQTSLETSIFTPSPCKIPPPTRVGFGSGQPPPYDHLFEVALPKTAHHFVIRKTEELLKKAKGNTEEDGVPSTSPMEVLDRLIQQGADAHSKELNKLPLPSKSVDWTHFGGSPPSDEIRTLRDQLLLLHNQLLYERFKRQQHALRNRRLLRKVIKAAALEEHNAAMKDQLKLQEKDIQMWKVSLQKEQARYNQLQEQRDTMVTKLHSQIRQLQHDREEFYNQSQELQTKLEDCRNMIAELRIELKKANNKVCHTELLLSQVSQKLSNSESVQQQMEFLNRQLLVLGEVNELYLEQLQNKHSDTTKEVEMMKAAYRKELEKNRSHVLQQTQRLDTSQKRILELESHLAKKDHLLLEQKKYLEDVKLQARGQLQAAESRYEAQKRITQVFELEILDLYGRLEKDGLLKKLEEEKAEAAEAAEERLDCCNDGCSDSMVGHNEEASGHNGETKTPRPSSARGSSGSRGGGGSSSSSSELSTPEKPPHQRAGPFSSRWETTMGEASASIPTTVGSLPSSKSFLGMKARELFRNKSESQCDEDGMTSSLSESLKTELGKDLGVEAKIPLNLDGPHPSPPTPDSVGQLHIMDYNETHHEHSGTKLGPEQKLISEEDLNSAVDHHHHHH  
s2:
MNLLPCNPHGNGLLYAGFNQDHGCFACGMENGFRVYNTDPLKEKEKQEFLEGGVGHVEMLFRCNYLALVGGGKKPKYPPNKVMIWDDLKKKTVIEIEFSTEVKAVKLRRDRIVVVLDSMIKVFTFTHNPHQLHVFETCYNPKGLCVLCPNSNNSLLAFPGTHT....GHVQLVDLASTEKPPVDIPAHEGVLSCIALNLQGTRIATAS.EKGTLIRIFDTSSGHLIQELRRGSQAANIYCINFNQDASLICVSSDHGTVHIFAAEDPKRNKQSSLASASFLPKYFSSKWSFSKFQVPSGSPCICAFGTEPNAVIAICADGSYYKFLFNPKGECIRDVYAQFLEMTDDKL...............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................  
s1:
..........................................................................MAQQANVGELLAMLDSPMLGVRDDVTAVFKENLNSDRGPMLVNTLVDYYLETSSQPALHILTTLQEPHDKHLLDRINEYVGKAATRLSILSLLGHVIRLQ.PSWKHKLSQAPLLPSLLKCLKMDTDVVVLTTGVLVLITMLPMIPQSGKQHLLDFFDIFGRLSSWCLKKPGHVAEVYLVHLHASVYALFHRLYGM...YPCNFVSFLRSHYSMKENLETFEEVVKPMMEHV.RIHPELV.....TGSKDHEL.DPRRWKRLETHDVVIECAKISLDPTEASYEDGYSVSHQISARFPHRSADVTTSPYADTQNSYGCATSTPYSTSRLMLLNMPGQLPQTLSSPSTRLITEPPQATLWSPSMVCGMTTPPTSPGNVPPDLSHPYSKVFGTTAGGKGTPLGTPATSPPPAPLCHSDDYVHISLPQATVTPPRKEERMDSARPCLHRQHHLLNDRGSEEPPGSKGSVTLSDLPGFLGDLASEEDSIEKDKEEAAISRELSEITTAEAEPVVPRGGFDSPFYRDSLPGSQRKTHSAASSSQGASVNPEPLHSSLDKLGPDTPKQAFTPIDLPCGSADESPAGDRECQTSLETSIFTPSPCKIPPPTRVGFGSGQPPPYDHLFEVALPKTAHHFVIRKTEELLKKAKGNTEEDGVPSTSPMEVLDRLIQQGADAHSKELNKLPLPSKSVDWTHFGGSPPSDEIRTLRDQLLLLHNQLLYERFKRQQHALRNRRLLRKVIKAAALEEHNAAMKDQLKLQEKDIQMWKVSLQKEQARYNQLQEQRDTMVTKLHSQIRQLQHDREEFYNQSQELQTKLEDCRNMIAELRIELKKANNKVCHTELLLSQVSQKLSNSESVQQQMEFLNRQLLVLGEVNELYLEQLQNKHSDTTKEVEMMKAAYRKELEKNRSHVLQQTQRLDTSQKRILELESHLAKKDHLLLEQKKYLEDVKLQARGQLQAAESRYEAQKRITQVFELEILDLYGRLEKDGLLKKLEEEKAEAAEAAEERLDCCNDGCSDSMVGHNEEASGHNGETKTPRPSSARGSSGSRGGGGSSSSSSELSTPEKPPHQRAGPFSSRWETTMGEASASIPTTVGSLPSSKSFLGMKARELFRNKSESQCDEDGMTSSLSESLKTELGKDLGVEAKIPLNLDGPHPSPPTPDSVGQLHIMDYNETHHEHSGTKLGPEQKLISEEDLNSAVDHHHHHH  
s2:
MNLLPCNPHGNGLLYAGFNQDHGCFACGMENGFRVYNTDPLKEKEKQEFLEGGVGHVEMLFRCNYLALVGGGKKPKYPPNKVMIWDDLKKKTVIEIEFSTEVKAVKLRRDRIVVVLDSMIKVFTFTHNPHQLHVFETCYNPKGLCVLCPNSNNSLLAFPGTHT....GHVQLVDLASTEKPPVDIPAHEGVLSCIALNLQGTRIATAS.EKGTLIRIFDTSSGHLIQELRRGSQAANIYCINFNQDASLICVSSDHGTVHIFAAEDPKRNKQSSLASASFLPKYFSSKWSFSKFQVPSGSPCICAFGTEPNAVIAICADGSYYKFLFNPKGECIRDVYAQFLEMTDDKL...............................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................................  
s1:
........................MTEDSQRNFRSVYYEKVGFRGVEEKKSLEILLKD.DRLDTEKLCTFSQRF.....PLPSMYRALVWKVL..LGILPPHHESHAKVMMYRKEQYLDVLHALKVVRFVSDATPQAEVYLRMYQLES..GKLPRSP....SFPLEPDDEVFLAIAKAMEEMVEDSVDCYWITRRFVNQLNTKYRDSLPQLPKAFEQYLNLEDGRLLTHLRMCSAAPKLPYDLWFKR.....CFA...GCL....PESSLQRVWDKVVSGSCKILVFVAVEILLTFKIKVMALNSAEKITKFLEN...IPQDSSDAIVSKAIDLWHKHCGTPVHSSDYKDDDDK.  
s2:
MNLLPCNPHGNGLLYAGFNQDHGCFACGMENGFRVYNTDP.....LKEKEKQEFLEGGVGHVEMLFRCNYLALVGGGKKPKYPPNKVMIWDDLKKKTVIEIEFSTEVKAVKLRRDRIVVVLDSMIKVFTFTHNPHQLHVFETCYNPKGLCVLCPNSNNSLLAFPGTHTGHVQLVDLASTEKPPVDIPAHEGVLSCIALNLQGT.RIATASEKGTLIRIFDTSSGHLIQELRRGSQAAN.IYCINFNQDASLICVSSDHGTVHIFAAEDPKRNKQSSLASASFLPKYFSSKWSFSKFQVP....SGSPCICAFGTEPNAVIAICADGSYYKFLFNPKGECIRDVYAQFLEMTDDKL  
s1:
....MHHHHHHGLLYAGFNQDHGCFACGMENGFRVYNTDPLKEKEKQEFLEGGVGHVEMLFRCNYLALVGGGKK......KVMIWDDLKKKTVIEIEFSTEVKAVKLRRDRIVVVLDSMIKVFTFTHNPHQLHVFETCYNPKGLCVLCPNSNNSLLAFPGTHTGHVQLVDLASTEKPPVDIPAHEGVLSCIALNLQGTRIATASEKGTLIRIFDTSSGHLIQELRRGSQAANIYCINFNQDASLICVSSDHGTVHIFAAEDPK..................SKWSFSKFQVPSGSPCICAFGTEPNAVIAICADGSYYKFLFNPKGECIRDVYAQFLEMTDDKL  
s2:
MNLLPCNPHGNGLLYAGFNQDHGCFACGMENGFRVYNTDPLKEKEKQEFLEGGVGHVEMLFRCNYLALVGGGKKPKYPPNKVMIWDDLKKKTVIEIEFSTEVKAVKLRRDRIVVVLDSMIKVFTFTHNPHQLHVFETCYNPKGLCVLCPNSNNSLLAFPGTHTGHVQLVDLASTEKPPVDIPAHEGVLSCIALNLQGTRIATASEKGTLIRIFDTSSGHLIQELRRGSQAANIYCINFNQDASLICVSSDHGTVHIFAAEDPKRNKQSSLASASFLPKYFSSKWSFSKFQVPSGSPCICAFGTEPNAVIAICADGSYYKFLFNPKGECIRDVYAQFLEMTDDKL  
s1:
............................................................................................................................................................................................................................................................................................................................................????????????  
s2:
MNLLPCNPHGNGLLYAGFNQDHGCFACGMENGFRVYNTDPLKEKEKQEFLEGGVGHVEMLFRCNYLALVGGGKKPKYPPNKVMIWDDLKKKTVIEIEFSTEVKAVKLRRDRIVVVLDSMIKVFTFTHNPHQLHVFETCYNPKGLCVLCPNSNNSLLAFPGTHTGHVQLVDLASTEKPPVDIPAHEGVLSCIALNLQGTRIATASEKGTLIRIFDTSSGHLIQELRRGSQAANIYCINFNQDASLICVSSDHGTVHIFAAEDPKRNKQSSLASASFLPKYFSSKWSFSKFQVPSGSPCICAFGTEPNAVIAICADGSYYKFLFNPKGECIRDVYAQFLEMTDDKL  
s1:
............................................................................................................................................................................................................................................................................................................................................????????????  
s2:
MNLLPCNPHGNGLLYAGFNQDHGCFACGMENGFRVYNTDPLKEKEKQEFLEGGVGHVEMLFRCNYLALVGGGKKPKYPPNKVMIWDDLKKKTVIEIEFSTEVKAVKLRRDRIVVVLDSMIKVFTFTHNPHQLHVFETCYNPKGLCVLCPNSNNSLLAFPGTHTGHVQLVDLASTEKPPVDIPAHEGVLSCIALNLQGTRIATASEKGTLIRIFDTSSGHLIQELRRGSQAANIYCINFNQDASLICVSSDHGTVHIFAAEDPKRNKQSSLASASFLPKYFSSKWSFSKFQVPSGSPCICAFGTEPNAVIAICADGSYYKFLFNPKGECIRDVYAQFLEMTDDKL  

> isolde restrain distances "#1.2/F" templateAtoms "#2.6/F" perChain false
> adjustForConfidence true useCoordinateAlignment false kappa 4.40 fallOff
> 2.50 groupName "Reference Distance Restraints"

ISOLDE: Checking and correcting nomenclature for (pseudo)symmetric side
chains...  
[Repeated 1 time(s)]ISOLDE: Corrected atom nomenclature of 44 residues in
model #2.6 to IUPAC-IUB standards.  
Computing secondary structure  
[Repeated 1 time(s)]

> isolde restrain torsions #1.2/F templateResidues #2.6/F adjustForConfidence
> true sidechains true springConstant 250.00 alpha 0.20

ISOLDE: Checking and correcting nomenclature for (pseudo)symmetric side
chains...  
[Repeated 1 time(s)]Computing secondary structure  
[Repeated 1 time(s)]

> sequence chain #1/F

Alignment identifier is 1.2/F  

> select clear

> hide #2.6 models

> select #1/F

4718 atoms, 4773 bonds, 305 residues, 1 model selected  

> isolde sim start #1.2/F

ISOLDE: started sim  

> select clear

> isolde sim pause

> isolde sim resume

> show #2.6 models

> isolde sim pause

> show #2/F

> hide #2.6 models

> sequence align #1/F,#2/F

Alignment identifier is 1  
Associated 9ce3 (1.2) chain F to #1.2/F with 0 mismatches  
Associated 9ce3 (1.2) chain G to #1.2/F with 0 mismatches  
Associated 9ce3 (1.2) chain H to #1.2/F with 0 mismatches  
Associated AlphaFold WIPI3_HUMAN chain F (2.6) chain F to #2.6/F with 0
mismatches  
Associated 9ce3 chain F to #1.2/F with 0 mismatches  
Associated 9ce3 chain G to #1.2/F with 0 mismatches  
Associated 9ce3 chain H to #1.2/F with 0 mismatches  
Associated 7dl2 chain F to #1.2/F with 0 mismatches  
Associated working.pdb chain F to #1.2/F with 0 mismatches  
Associated working.pdb chain G to #1.2/F with 0 mismatches  
Associated working.pdb chain H to #1.2/F with 0 mismatches  
Showing conservation header ("seq_conservation" residue attribute) for
alignment 1  
Webservices job id: 6VZNKMRYQOWJL311  

> select up

22 atoms, 21 bonds, 1 residue, 2 models selected  

> select up

161 atoms, 164 bonds, 10 residues, 2 models selected  

> ra

> isolde sim resume

> isolde sim pause

> isolde sim resume

> isolde sim pause

> select #1.2/F-H #3/F-H #4/F #6/F-H

13291 atoms, 13441 bonds, 8 pseudobonds, 1190 residues, 5 models selected  

> select #1.2/F:75 #3/F:75 #4/F:71 #6/F:75

58 atoms, 54 bonds, 4 residues, 4 models selected  

> select #1.2/F:75-76 #3/F:75-76 #4/F:71-72 #6/F:75-76

102 atoms, 98 bonds, 8 residues, 4 models selected  
Clustal Omega Alignment [ID: 1] region #1.2/F [81-82] RMSD: 34.447  
  

> view sel

> view #1&sel

> select #1.2/F:75 #3/F:75 #4/F:71 #6/F:75

58 atoms, 54 bonds, 4 residues, 4 models selected  

> select #1.2/F:75-94 #3/F:75-94 #4/F:71-90 #6/F:75-94

969 atoms, 974 bonds, 80 residues, 4 models selected  
Clustal Omega Alignment [ID: 1] region #1.2/F [81-100] RMSD: 24.083  
  

> select #1.2/F:75 #3/F:75 #4/F:71 #6/F:75

58 atoms, 54 bonds, 4 residues, 4 models selected  

> select #1.2/F:75-76 #3/F:75-76 #4/F:71-72 #6/F:75-76

102 atoms, 98 bonds, 8 residues, 4 models selected  
Clustal Omega Alignment [ID: 1] region #1.2/F [81-82] RMSD: 34.447  
  

> select up

17 atoms, 16 bonds, 1 residue, 1 model selected  

> select up

7 atoms, 6 bonds, 1 residue, 2 models selected  

> select up

65 atoms, 64 bonds, 5 residues, 2 models selected  

> select #1.2/F:71 #3/F:71 #6/F:71

18 atoms, 15 bonds, 3 residues, 3 models selected  

> select #1.2/F:71-80 #3/F:71-80 #4/F:69-76 #6/F:71-80

456 atoms, 458 bonds, 38 residues, 4 models selected  
Clustal Omega Alignment [ID: 1] region #1.2/F [71-86] RMSD: 30.899  
  

> select #1.2/F:67 #3/F:67 #4/F:63 #6/F:67

30 atoms, 26 bonds, 4 residues, 4 models selected  

> select #1.2/F:67-70 #3/F:67-70 #4/F:63-65 #6/F:67-70

143 atoms, 139 bonds, 15 residues, 4 models selected  
Clustal Omega Alignment [ID: 1] region #1.2/F [67-70] RMSD: 40.603  
  

> show #2.6 models

> select up

7 atoms, 6 bonds, 1 residue, 2 models selected  

> select up

65 atoms, 64 bonds, 5 residues, 2 models selected  

> rd

> ar

Unknown command: ar  

> ra

> hide #2.6 models

> isolde sim resume

> isolde pepflip #1.2/F:74

> select up

20 atoms, 20 bonds, 1 residue, 1 model selected  

> rt

> isolde sim pause

> isolde sim stop

Sim termination reason: None  
ISOLDE: Checking and correcting nomenclature for (pseudo)symmetric side
chains...  
ISOLDE: Corrected atom nomenclature of 6 residues in model #1.2 to IUPAC-IUB
standards.  
ISOLDE: stopped sim  

> isolde sim start #1.2/F:103

ISOLDE: started sim  

> select clear

> isolde sim stop

Sim termination reason: None  
ISOLDE: Checking and correcting nomenclature for (pseudo)symmetric side
chains...  
ISOLDE: Corrected atom nomenclature of 4 residues in model #1.2 to IUPAC-IUB
standards.  
ISOLDE: stopped sim  

> save working.cxs

Taking snapshot of stepper: 9ce3  

> ui tool show Shell

[Repeated 1 time(s)]

> sequence chain #1/A

Alignment identifier is 1.2/A  

> st

[Repeated 3 time(s)]

> st /A

Multiple residues selected! Going to the first...  

> st

[Repeated 54 time(s)]

> isolde sim start #1.2/A:90

ISOLDE: started sim  

> isolde sim stop

Sim termination reason: None  
ISOLDE: Checking and correcting nomenclature for (pseudo)symmetric side
chains...  
ISOLDE: stopped sim  

> isolde sim start #1.2/A:87-93

ISOLDE: started sim  

> isolde sim stop

Sim termination reason: None  
ISOLDE: Checking and correcting nomenclature for (pseudo)symmetric side
chains...  
ISOLDE: stopped sim  

> ~cartoon

> cartoon

> ~cartoon sel

> cartoon

> ~cartoon sel

> cartoon

> ~cartoon sel

> cartoon

> select clear




OpenGL version: 3.3.0 NVIDIA 535.183.06
OpenGL renderer: NVIDIA GeForce RTX 3070/PCIe/SSE2
OpenGL vendor: NVIDIA Corporation

Python: 3.11.4
Locale: en_GB.UTF-8
Qt version: PyQt6 6.7.1, Qt 6.7.1
Qt runtime version: 6.7.3
Qt platform: xcb

XDG_SESSION_TYPE=x11
DESKTOP_SESSION=ubuntu
XDG_SESSION_DESKTOP=ubuntu
XDG_CURRENT_DESKTOP=ubuntu:GNOME
DISPLAY=:1
Manufacturer: Dell Inc.
Model: XPS 8950
OS: Ubuntu 22.04
Architecture: 64bit ELF
Virtual Machine: none
CPU: 20 12th Gen Intel(R) Core(TM) i7-12700
Cache Size: 25600 KB
Memory:
	               total        used        free      shared  buff/cache   available
	Mem:            31Gi        29Gi       495Mi       145Mi       759Mi       683Mi
	Swap:          2.0Gi       2.0Gi       2.0Mi

Graphics:
	0000:01:00.0 VGA compatible controller [0300]: NVIDIA Corporation GA104 [GeForce RTX 3070 Lite Hash Rate] [10de:2488] (rev a1)	
	Subsystem: Dell GA104 [GeForce RTX 3070 Lite Hash Rate] [1028:c903]	
	Kernel driver in use: nvidia

Installed Packages:
    alabaster: 1.0.0
    anyio: 4.7.0
    appdirs: 1.4.4
    asttokens: 3.0.0
    auditwheel: 6.1.0
    autocommand: 2.2.2
    babel: 2.16.0
    backports.tarfile: 1.2.0
    beautifulsoup4: 4.12.3
    blockdiag: 3.0.0
    blosc2: 3.0.0
    build: 1.2.1
    certifi: 2024.8.30
    cftime: 1.6.4.post1
    charset-normalizer: 3.4.0
    ChimeraX-AddCharge: 1.5.18
    ChimeraX-AddH: 2.2.6
    ChimeraX-AlignmentAlgorithms: 2.0.2
    ChimeraX-AlignmentHdrs: 3.5
    ChimeraX-AlignmentMatrices: 2.1
    ChimeraX-Alignments: 2.16.1
    ChimeraX-AlphaFold: 1.0.1
    ChimeraX-AltlocExplorer: 1.1.2
    ChimeraX-AmberInfo: 1.0
    ChimeraX-Arrays: 1.1
    ChimeraX-Atomic: 1.58.8
    ChimeraX-AtomicLibrary: 14.1.11
    ChimeraX-AtomSearch: 2.0.1
    ChimeraX-AxesPlanes: 2.4
    ChimeraX-BasicActions: 1.1.2
    ChimeraX-BILD: 1.0
    ChimeraX-BlastProtein: 3.0.0
    ChimeraX-BondRot: 2.0.4
    ChimeraX-BugReporter: 1.0.1
    ChimeraX-BuildStructure: 2.13.1
    ChimeraX-Bumps: 1.0
    ChimeraX-BundleBuilder: 1.4.0
    ChimeraX-ButtonPanel: 1.0.1
    ChimeraX-CageBuilder: 1.0.1
    ChimeraX-CellPack: 1.0
    ChimeraX-Centroids: 1.4
    ChimeraX-ChangeChains: 1.1
    ChimeraX-CheckWaters: 1.4
    ChimeraX-ChemGroup: 2.0.1
    ChimeraX-Clashes: 2.3
    ChimeraX-Clipper: 0.24.0
    ChimeraX-ColorActions: 1.0.5
    ChimeraX-ColorGlobe: 1.0
    ChimeraX-ColorKey: 1.5.6
    ChimeraX-CommandLine: 1.2.5
    ChimeraX-ConnectStructure: 2.0.1
    ChimeraX-Contacts: 1.0.1
    ChimeraX-Core: 1.9
    ChimeraX-CoreFormats: 1.2
    ChimeraX-coulombic: 1.4.4
    ChimeraX-Crosslinks: 1.0
    ChimeraX-Crystal: 1.0
    ChimeraX-CrystalContacts: 1.0.1
    ChimeraX-DataFormats: 1.2.3
    ChimeraX-Dicom: 1.2.6
    ChimeraX-DistMonitor: 1.4.2
    ChimeraX-DockPrep: 1.1.3
    ChimeraX-Dssp: 2.0
    ChimeraX-EMDB-SFF: 1.0
    ChimeraX-ESMFold: 1.0
    ChimeraX-FileHistory: 1.0.1
    ChimeraX-FunctionKey: 1.0.1
    ChimeraX-Geometry: 1.3
    ChimeraX-gltf: 1.0
    ChimeraX-Graphics: 1.4.1
    ChimeraX-Hbonds: 2.5
    ChimeraX-Help: 1.3
    ChimeraX-HKCage: 1.3
    ChimeraX-IHM: 1.1
    ChimeraX-ImageFormats: 1.2
    ChimeraX-IMOD: 1.0
    ChimeraX-IO: 1.0.3
    ChimeraX-ISOLDE: 1.9
    ChimeraX-ItemsInspection: 1.0.1
    ChimeraX-IUPAC: 1.0
    ChimeraX-KVFinder: 1.2.1
    ChimeraX-Label: 1.1.14
    ChimeraX-LinuxSupport: 1.0.1
    ChimeraX-ListInfo: 1.2.2
    ChimeraX-Log: 1.2
    ChimeraX-LookingGlass: 1.1
    ChimeraX-Maestro: 1.9.1
    ChimeraX-Map: 1.3
    ChimeraX-MapData: 2.0
    ChimeraX-MapEraser: 1.0.1
    ChimeraX-MapFilter: 2.0.1
    ChimeraX-MapFit: 2.0
    ChimeraX-MapSeries: 2.1.1
    ChimeraX-Markers: 1.0.1
    ChimeraX-Mask: 1.0.2
    ChimeraX-MatchMaker: 2.1.6
    ChimeraX-MCopy: 1.0
    ChimeraX-MDcrds: 2.7.2
    ChimeraX-MedicalToolbar: 1.1
    ChimeraX-Meeting: 1.0.1
    ChimeraX-MLP: 1.1.1
    ChimeraX-mmCIF: 2.14.2
    ChimeraX-MMTF: 2.2
    ChimeraX-ModelArchive: 1.0
    ChimeraX-Modeller: 1.5.18
    ChimeraX-ModelPanel: 1.5
    ChimeraX-ModelSeries: 1.0.1
    ChimeraX-Mol2: 2.0.3
    ChimeraX-Mole: 1.0
    ChimeraX-Morph: 1.0.2
    ChimeraX-MouseModes: 1.2
    ChimeraX-Movie: 1.0
    ChimeraX-MutationScores: 1.0
    ChimeraX-Neuron: 1.0
    ChimeraX-Nifti: 1.2
    ChimeraX-NMRSTAR: 1.0.2
    ChimeraX-NRRD: 1.2
    ChimeraX-Nucleotides: 2.0.3
    ChimeraX-OpenCommand: 1.14
    ChimeraX-OrthoPick: 1.0.1
    ChimeraX-PDB: 2.7.6
    ChimeraX-PDBBio: 1.0.1
    ChimeraX-PDBLibrary: 1.0.4
    ChimeraX-PDBMatrices: 1.0
    ChimeraX-PickBlobs: 1.0.1
    ChimeraX-Positions: 1.0
    ChimeraX-PresetMgr: 1.1.2
    ChimeraX-PubChem: 2.2
    ChimeraX-QScore: 1.2
    ChimeraX-ReadPbonds: 1.0.1
    ChimeraX-Registration: 1.1.2
    ChimeraX-RemoteControl: 1.0
    ChimeraX-RenderByAttr: 1.6.2
    ChimeraX-RenumberResidues: 1.1
    ChimeraX-ResidueFit: 1.0.1
    ChimeraX-RestServer: 1.3.1
    ChimeraX-RNALayout: 1.0
    ChimeraX-RotamerLibMgr: 4.0
    ChimeraX-RotamerLibsDunbrack: 2.0
    ChimeraX-RotamerLibsDynameomics: 2.0
    ChimeraX-RotamerLibsRichardson: 2.0
    ChimeraX-SaveCommand: 1.5.1
    ChimeraX-SchemeMgr: 1.0
    ChimeraX-SDF: 2.0.2
    ChimeraX-Segger: 1.0
    ChimeraX-Segment: 1.0.1
    ChimeraX-Segmentations: 3.5.6
    ChimeraX-SelInspector: 1.0
    ChimeraX-SeqView: 2.14
    ChimeraX-Shape: 1.0.1
    ChimeraX-Shell: 1.0.1
    ChimeraX-Shortcuts: 1.2.0
    ChimeraX-ShowSequences: 1.0.3
    ChimeraX-SideView: 1.0.1
    ChimeraX-SimilarStructures: 1.0.1
    ChimeraX-Smiles: 2.1.2
    ChimeraX-SmoothLines: 1.0
    ChimeraX-SpaceNavigator: 1.0
    ChimeraX-StdCommands: 1.18.1
    ChimeraX-STL: 1.0.1
    ChimeraX-Storm: 1.0
    ChimeraX-StructMeasure: 1.2.1
    ChimeraX-Struts: 1.0.1
    ChimeraX-Surface: 1.0.1
    ChimeraX-SwapAA: 2.0.1
    ChimeraX-SwapRes: 2.5
    ChimeraX-TapeMeasure: 1.0
    ChimeraX-TaskManager: 1.0
    ChimeraX-Test: 1.0
    ChimeraX-Toolbar: 1.2.3
    ChimeraX-ToolshedUtils: 1.2.4
    ChimeraX-Topography: 1.0
    ChimeraX-ToQuest: 1.0
    ChimeraX-Tug: 1.0.1
    ChimeraX-UI: 1.41
    ChimeraX-Umap: 1.0
    ChimeraX-uniprot: 2.3.1
    ChimeraX-UnitCell: 1.0.1
    ChimeraX-ViewDockX: 1.4.4
    ChimeraX-VIPERdb: 1.0
    ChimeraX-Vive: 1.1
    ChimeraX-VolumeMenu: 1.0.1
    ChimeraX-vrml: 1.0
    ChimeraX-VTK: 1.0
    ChimeraX-WavefrontOBJ: 1.0
    ChimeraX-WebCam: 1.0.2
    ChimeraX-WebServices: 1.1.4
    ChimeraX-Zone: 1.0.1
    colorama: 0.4.6
    comm: 0.2.2
    contourpy: 1.3.1
    cxservices: 1.2.3
    cycler: 0.12.1
    Cython: 3.0.10
    debugpy: 1.8.9
    decorator: 5.1.1
    distro: 1.9.0
    docutils: 0.21.2
    executing: 2.1.0
    filelock: 3.15.4
    fonttools: 4.55.3
    funcparserlib: 2.0.0a0
    glfw: 2.8.0
    grako: 3.16.5
    h11: 0.14.0
    h5py: 3.12.1
    html2text: 2024.2.26
    httpcore: 1.0.7
    httpx: 0.28.1
    idna: 3.10
    ihm: 1.3
    imagecodecs: 2024.6.1
    imagesize: 1.4.1
    importlib_metadata: 8.0.0
    importlib_resources: 6.4.0
    inflect: 7.3.1
    ipykernel: 6.29.5
    ipython: 8.26.0
    ipywidgets: 8.1.5
    jaraco.context: 5.3.0
    jaraco.functools: 4.0.1
    jaraco.text: 3.12.1
    jedi: 0.19.1
    Jinja2: 3.1.4
    jupyter_client: 8.6.2
    jupyter_core: 5.7.2
    jupyterlab_widgets: 3.0.13
    kiwisolver: 1.4.7
    line_profiler: 4.1.3
    lxml: 5.2.2
    lz4: 4.3.3
    MarkupSafe: 3.0.2
    matplotlib: 3.9.2
    matplotlib-inline: 0.1.7
    more-itertools: 10.3.0
    msgpack: 1.0.8
    ndindex: 1.9.2
    nest-asyncio: 1.6.0
    netCDF4: 1.6.5
    networkx: 3.3
    nibabel: 5.2.0
    nptyping: 2.5.0
    numexpr: 2.10.2
    numpy: 1.26.4
    openvr: 1.26.701
    ordered-set: 4.1.0
    packaging: 23.2
    packaging: 24.1
    ParmEd: 4.2.2
    parso: 0.8.4
    pep517: 0.13.1
    pexpect: 4.9.0
    pillow: 10.4.0
    pip: 24.2
    pkginfo: 1.11.1
    platformdirs: 4.3.6
    platformdirs: 4.2.2
    prompt_toolkit: 3.0.48
    psutil: 6.0.0
    ptyprocess: 0.7.0
    pure_eval: 0.2.3
    py-cpuinfo: 9.0.0
    pycollada: 0.8
    pydicom: 2.4.4
    pyelftools: 0.31
    Pygments: 2.18.0
    pynmrstar: 3.3.4
    pynrrd: 1.0.0
    PyOpenGL: 3.1.7
    PyOpenGL-accelerate: 3.1.7
    pyopenxr: 1.0.3401
    pyparsing: 3.2.0
    pyproject_hooks: 1.2.0
    PyQt6-commercial: 6.7.1
    PyQt6-Qt6: 6.7.3
    PyQt6-WebEngine-commercial: 6.7.0
    PyQt6-WebEngine-Qt6: 6.7.3
    PyQt6-WebEngineSubwheel-Qt6: 6.7.3
    PyQt6_sip: 13.8.0
    python-dateutil: 2.9.0.post0
    pytz: 2024.2
    pyzmq: 26.2.0
    qtconsole: 5.5.2
    QtPy: 2.4.2
    qtshim: 1.0
    RandomWords: 0.4.0
    requests: 2.32.3
    scipy: 1.14.0
    setuptools: 72.1.0
    sfftk-rw: 0.8.1
    six: 1.16.0
    sniffio: 1.3.1
    snowballstemmer: 2.2.0
    sortedcontainers: 2.4.0
    soupsieve: 2.6
    Sphinx: 8.0.2
    sphinx-autodoc-typehints: 2.2.3
    sphinxcontrib-applehelp: 2.0.0
    sphinxcontrib-blockdiag: 3.0.0
    sphinxcontrib-devhelp: 2.0.0
    sphinxcontrib-htmlhelp: 2.1.0
    sphinxcontrib-jsmath: 1.0.1
    sphinxcontrib-qthelp: 2.0.0
    sphinxcontrib-serializinghtml: 2.0.0
    stack-data: 0.6.3
    superqt: 0.6.3
    tables: 3.10.1
    tcia_utils: 1.5.1
    tifffile: 2024.7.24
    tinyarray: 1.2.4
    tomli: 2.0.1
    tornado: 6.4.2
    traitlets: 5.14.3
    typeguard: 4.3.0
    typing_extensions: 4.12.2
    typing_extensions: 4.12.2
    tzdata: 2024.2
    urllib3: 2.2.3
    wcwidth: 0.2.13
    webcolors: 24.6.0
    wheel: 0.43.0
    wheel: 0.43.0
    wheel-filename: 1.4.1
    widgetsnbextension: 4.0.13
    zipp: 3.19.2

Attachments (1)

memleak_test.py (130 bytes ) - added by Tom Goddard 10 months ago.: Python to select and unselect 5000 times without using ChimeraX command parsing.

Download all attachments as: .zip

Change History (30)

comment:1 by Tristan Croll, 10 months ago

Can't seem to replicate this in a fresh session - even one restored from
the same .cxs. Weird.

On Wed, Jan 8, 2025 at 11:49 AM ChimeraX <ChimeraX-bugs-admin@cgl.ucsf.edu>
wrote:

>

comment:2 by Tristan Croll, 10 months ago

So there *does* seem to be a memory leak, but (a) I'm not sure it has
anything to do with ribbon.py *per se*, and (b) as far as I can tell it's
invisible to tracemalloc. With a handful of large models open (e.g.
multiple copies of 9ce3) my system monitor shows ChimeraX's memory usage
gradually ticking upwards as I mess around (creating and destroying
cartoons, changing colouring etc.) but tracemalloc shows essentially no
change (other than the very occasional increment to opengl.py:2826) and so
far I've been unable to connect it to any specific thing I'm doing.

On Wed, Jan 8, 2025 at 12:03 PM ChimeraX <ChimeraX-bugs-admin@cgl.ucsf.edu>
wrote:

>
>
>
>

comment:3 by Eric Pettersen, 10 months ago

Cc:	chimera-programmers added
Component:	Unassigned → Performance
Description:	modified (diff)
Owner:	set to Tom Goddard
Platform:	→ all
Project:	→ ChimeraX
Status:	new → assigned
Summary:	ChimeraX bug report submission → Memory leak

comment:4 by Tom Goddard, 10 months ago

Owner:	changed from Tom Goddard to Tristan Croll

In a simple test I do not see the ribbon code leaking memory.

open 6vxf
sel /A:345-350
turn z 1 36000 atoms sel

The memory use does not increase as the ribbons are recomputed thousands of times.

I suspect this is something specific to ISOLDE. For instance if you create many temporary drawings and they get removed from the scene but not deleted then memory would keep going up. That is just speculation since I have no clue what ISOLDE is doing while the memory keeps increasing.

comment:5 by Tristan Croll, 10 months ago

Owner:	changed from Tristan Croll to Tom Goddard

Some more experimentation after sleeping on it... looks like it has something to do with colouring (or possibly something more general to do with getting/setting molarray properties?). To really show it up quickly I opened 50 copies of 9ce3 in a fresh ChimeraX session without starting ISOLDE. In that session, the command:

rainbow;wait 1;color bych

... loses me about a GB of RAM each time (not sure if the "wait 1" is actually necessary). tracemalloc shows what looks like an accumulation of large numbers of unreleased pointers:

import tracemalloc
tracemalloc.start()
before = tracemalloc.take_snapshot()
# one iteration of "rainbow;wait 1; color bych
snap1 = tracemalloc.take_snapshot()

top_stats1 = snap1.compare_to(before, 'lineno')

for stat in top_stats1[:5]:
    print(stat)
/usr/lib/ucsf-chimerax/lib/python3.11/ctypes/__init__.py:512: size=164 MiB (+164 MiB), count=1757537 (+1757000), average=98 B
/usr/lib/ucsf-chimerax/lib/python3.11/site-packages/numpy/core/_internal.py:283: size=140 MiB (+140 MiB), count=875803 (+875803), average=168 B
/usr/lib/ucsf-chimerax/lib/python3.11/site-packages/chimerax/atomic/molc.py:207: size=120 MiB (+120 MiB), count=2407354 (+2407354), average=52 B
/usr/lib/ucsf-chimerax/lib/python3.11/site-packages/chimerax/core/undo.py:400: size=60.2 MiB (+60.2 MiB), count=656851 (+656851), average=96 B
/usr/lib/ucsf-chimerax/lib/python3.11/site-packages/numpy/core/_internal.py:255: size=57.1 MiB (+57.0 MiB), count=439887 (+439688), average=136 B

# after another iteration
snap2 = tracemalloc.take_snapshot()

top_stats2 = snap2.compare_to(before, 'lineno')

for stat in top_stats2[:5]:
    print(stat)
/usr/lib/ucsf-chimerax/lib/python3.11/ctypes/__init__.py:512: size=328 MiB (+328 MiB), count=3513462 (+3512925), average=98 B
/usr/lib/ucsf-chimerax/lib/python3.11/site-packages/numpy/core/_internal.py:283: size=281 MiB (+281 MiB), count=1751609 (+1751609), average=168 B
/usr/lib/ucsf-chimerax/lib/python3.11/site-packages/chimerax/atomic/molc.py:207: size=241 MiB (+241 MiB), count=4814609 (+4814609), average=52 B
/usr/lib/ucsf-chimerax/lib/python3.11/weakref.py:582: size=160 MiB (+160 MiB), count=1 (+1), average=160 MiB
/usr/lib/ucsf-chimerax/lib/python3.11/site-packages/chimerax/core/undo.py:400: size=120 MiB (+120 MiB), count=1311703 (+1311703), average=96 B

Looking at this, it struck me that maybe this was just accumulating in the undo cache, but "undo clear" doesn't free up the memory.

comment:6 by Tristan Croll, 10 months ago

Resolution:	→ can't reproduce
Status:	assigned → closed

Ugh. Never mind. Turns out that (a) tracemalloc itself uses oodles of memory under these circumstances; and (b) exactly when the memory is released after "undo clear" is quite variable. Repeating the above experiment with 10 models and without tracemalloc running stabilises at around 4.5 GB memory use. Will reopen if I find a scenario where I can *actually* reproduce it.

comment:7 by Greg Couch, 10 months ago

You might be able to get a clue by running ChimeraX.valgrind on Linux.

comment:8 by Tristan Croll, 10 months ago

Thanks - but so far I’ve been unable to come up with a scenario that
*actually* replicates the behaviour of that session… just various dead
ends. If I see it again, hopefully I’ll be able to pinpoint the action that
triggers it.

On Thu, 9 Jan 2025 at 18:45, ChimeraX <ChimeraX-bugs-admin@cgl.ucsf.edu>
wrote:

>
>

comment:9 by Tristan Croll, 10 months ago

Resolution:	can't reproduce
Status:	closed → reopened

Huh... as luck would have it, I happened to be doing something else entirely today which also triggered it (doing comparisons over a set of ~1000 models, with no ISOLDE involved - caused ChimeraX to be killed by the OOM killer). The culprit appears to be zombie references to Atoms.intra_bonds left behind with each instance of AtomSpec (possibly just the AtomSpecs themselves not being cleaned up, with intra_bonds just being the biggest thing visible to tracemalloc?).

To replicate:

from chimerax.core.commands import run
import tracemalloc
run(session, 'open 8qie') # or any large model - this is just a randomly-chosen recent ribosome
tracemalloc.start()
before = tracemalloc.take_snapshot()
for _ in range(100):
  run(session, 'sel #1;~sel')
after = tracemalloc.take_snapshot()
top_stats = after.compare_to(before, 'lineno')
for stat in top_stats[:10]:
  print(stat)

output on my Linux machine:

/usr/lib/ucsf-chimerax/lib/python3.11/site-packages/chimerax/atomic/molarray.py:667: size=167 MiB (+167 MiB), count=200 (+200), average=856 KiB
/usr/lib/ucsf-chimerax/lib/python3.11/site-packages/chimerax/atomic/molc.py:175: size=162 MiB (+162 MiB), count=1004 (+1004), average=165 KiB
/usr/lib/ucsf-chimerax/lib/python3.11/site-packages/chimerax/atomic/molarray.py:378: size=158 MiB (+158 MiB), count=200 (+200), average=807 KiB
/usr/lib/ucsf-chimerax/lib/python3.11/site-packages/chimerax/atomic/molarray.py:258: size=7507 KiB (+7507 KiB), count=420 (+420), average=17.9 KiB
/usr/lib/ucsf-chimerax/lib/python3.11/site-packages/parso/cache.py:145: size=4359 KiB (+4359 KiB), count=78662 (+78662), average=57 B
/usr/lib/ucsf-chimerax/lib/python3.11/site-packages/parso/pgen2/generator.py:349: size=600 KiB (+600 KiB), count=10348 (+10348), average=59 B
/usr/lib/ucsf-chimerax/lib/python3.11/site-packages/chimerax/atomic/molc.py:207: size=423 KiB (+423 KiB), count=114 (+114), average=3799 B
/usr/lib/ucsf-chimerax/lib/python3.11/ctypes/__init__.py:512: size=373 KiB (+339 KiB), count=4058 (+3662), average=94 B
/usr/lib/ucsf-chimerax/lib/python3.11/site-packages/parso/pgen2/grammar_parser.py:31: size=338 KiB (+338 KiB), count=8422 (+8422), average=41 B
/usr/lib/ucsf-chimerax/lib/python3.11/site-packages/numpy/core/_internal.py:283: size=231 KiB (+231 KiB), count=1402 (+1402), average=169 B

Some notes:

in an attempt to rule out influences from the undo stack, I first ran 'undo depth 1' and additionally ran the 'sel;~sel' command 30 times.
if I monitor memory usage with `psutil:
```
import psutil
process = psutil.Process()
current_memory_use = process.memory_info().rss
```
... then each time I run the above command loop it chews up another ~1.8 GB.

comment:10 by Tristan Croll, 10 months ago

Yeah - so according to the garbage collector, all the Objects instances arising from running commands are being kept alive by something - I'm sure you'll be faster than me at figuring out what that something is.

comment:11 by Tom Goddard, 10 months ago

Owner:	changed from Tom Goddard to Eric Pettersen
Status:	reopened → assigned

I run your script 5 times but open the ribosome structure before manually so there is only one copy and I see about 1 GB extra after 5 consecutive runs. Some memory is allocated and freed since I see it go up and then down each run. But it does seem to increase more than inspected even when I add in an "undo clear" after each select command.

Maybe Eric has some idea about it dince it has nothing to do with ISOLDE and it may be related to atomic models and it doesn't seem to be the graphics. Also Eric I think debugged some tricky memory leak issues and may have good techniques to figure it out. Memory leaks in Python are hard to track down.

comment:12 by Tristan Croll, 10 months ago

So ChimeraX.valgrind doesn't seem to be present in the ChimeraX distributions any more... but messing around a bit more with tracking objects using the Python gc module... I don't think the culprit is actually the Objects instances after all - they're kept alive because they add callbacks to the 'deleted' trigger for any models they reference - close those models and they go away, but the memory use stays. But if I use gc to count references to ChimeraX objects after running the "sel #1;~sel #1" command a couple hundred times then closing the model...

import gc
from collections import Counter
before_types = Counter([type(o) for o in gc.get_objects()])
sorted_before = list(sorted(before_types.items(), key=lambda i:i[1], reverse=True))
chimerax_types_before = [t for t in sorted_before if 'chimerax' in str(t[0])]

from chimerax.core.commands import run
run(session, 'open 8qje')
for _ in range(200):
  run(session, 'sel #1',~sel #1')
run(session, 'close #1')

after_types = Counter([type(o) for o in gc.get_objects()])
sorted_after = list(sorted(after_types.items(), key=lambda i:i[1], reverse=True))
chimerax_after = [t for t in sorted_after if 'chimerax' in str(t[0])]


chimerax_before[:10]
[(chimerax.graphics.gllist.AddGLCall, 1251),
 (chimerax.core.commands.cli._WordInfo, 513),
 (chimerax.core.toolshed.info.CommandInfo, 377),
 (chimerax.core.commands.cli._Defer, 362),
 (chimerax.core.commands.atomspec._Selector, 326),
 (chimerax.core.toolshed.info.SelectorInfo, 324),
 (chimerax.core.colors.Colormap, 311),
 (chimerax.core.colors.Color, 250),
 (chimerax.core.filehistory.FileSpec, 200),
 (chimerax.ui.widgets.tabbedtoolbar._ButtonInfo, 180)]


chimerax_after[:10]
[(chimerax.graphics.gllist.AddGLCall, 1251),
 (chimerax.core.commands.cli._WordInfo, 515),
 (chimerax.atomic.molc.LP_c_void_p, 508),
 (chimerax.atomic.molarray.Atoms, 419),
 (chimerax.atomic.molarray.LookupTable, 400),
 (chimerax.core.toolshed.info.CommandInfo, 377),
 (chimerax.core.commands.cli._Defer, 362),
 (chimerax.core.commands.atomspec._Selector, 326),
 (chimerax.core.toolshed.info.SelectorInfo, 324),
 (chimerax.core.colors.Colormap, 311)]

Noting the 400 references to `molarray.LookupTable'...

from chimerax.atomic import Atoms
obs = [o for o in gc.get_objects() if isinstance(o, Atoms)]
len([a for a in obs if a._lookup_table._size is not None])
  400
for a in obs:
    if a._lookup_table._size is not None:
    print(a._lookup_table._size)
    break
  206516

Upshot: it looks like the __del__ method of molarray.LookupTable is not being called... possibly because of a circular reference back to its parent Collection?

comment:13 by Tristan Croll, 10 months ago

So that doesn't seem to be the cause either:

the accumulation of Atoms objects in the garbage collector only seems to happen if I use chimerax.core.commands.run() to run the "sel #1;~sel #1", but if I open a model in a fresh session and just use the command line to do:

perframe "sel #1; ~sel #1"

... and watch on my system monitor I see ChimeraX's memory use ticking up indefinitely until I use "perframe stop" (and it doesn't go back down when I close the model).

I tried making the LookupTable._collection a weakref.proxy, but that didn't do anything particularly useful.

Still getting nothing out of tracemalloc. Think it's time for me to give up and leave it to you.

comment:14 by Tristan Croll, 10 months ago

OK, one last point: it's not all that new. Tried rolling back to ChimeraX on my Windows machine, and tracking memory usage in the Task Manager:

ChimeraX fresh start: 326.8 MB

open 8qje

542.0 MB

undo depth 1
perframe "sel #1; ~sel #1" frames 50

2367.8 MB

close #1

2021.9 MB

... so a net leak of 1695.1 MB, or about 17 MB per individual "sel" command for this model.

I'm thinking the reason I haven't noticed this until now is (a) it's been a while since I did a really long-running session on a large model, and (b) moderately recently I rejigged ISOLDE's simulation start toolbar button to run via the command "isolde sim start {concise residue spec}" to give an echo to the log, so it's generating a *lot* more commands involving atomspecs than it used to.

comment:15 by Tom Goddard, 10 months ago

I get much smaller memory increases on Mac, but still certainly looks like a memory leak. The memory leak appears to be in command parsing with atom specifiers.

The following increases memory use from 430 MB to 2.2 GB in my test, so 3.6 Mbytes increase per frame. Tristan sees a similar increase on Linux in just 50 frames!

open 8qje
perframe "sel ; ~sel" frames 5000

But if instead I open a volume then the memory increase is neglibible, 370 MB -> 440 MB:

open 1080 from emdb
perframe "sel ; ~sel" frames 5000

But if I open a structure that is 35x bigger 8qie with 206,000 atoms instead of 8qje with 5600 atoms, I get a memory increase 515 MB -> 10 GB in 800 frames, or 12 MB per frame, only about 3 times bigger memory leak.

open 8qie
perframe "sel ; ~sel" frames 800

Returning to the smaller structure 8qje and running the select / unselect from Python instead of a command increases memory only 430 MB -> 460 MB.

from chimerax.std_commands.select import select, select_clear
for i in range(5000):
    select(session)
    select_clear(session)

So it seems the memory use is in command and atom specifier parsing. Trying instead of select and unselect using a different command "measure center #1" shows the same memory increase of 430 MB -> 2 GB

open 8qje
perframe "measure center #1" frames 5000

comment:16 by Tristan Croll, 10 months ago

Looks like the difference between my observation and Tom's is the presence or absence of the explicit "#1" in my commands. On my Windows machine with 8qje:

perframe "sel; ~sel" frames 50

raises memory use by only a small amount (small enough to be lost in the general noise of Python memory management). But:

perframe "sel #1; ~sel #1" frames 50

... performed immediately after in the same session leaks about 1.5 GB, as before. Seems like an important lead...

comment:17 by Tom Goddard, 10 months ago

On the same Mac Studio with ChimeraX 1.9 that I tested on in comment 15 the memory use including "#1" in the select commands versus omitting it is the same, 420 MB -> 2.2 GB

open 8qje
perframe "sel #1; ~sel #1" frames 5000

When the #1 is omitted then the parser of atom specifiers is not used. So it seems that just executing thousands of commands is the key ingredient to make the memory increase. I think executing each command causes some triggers to fire and maybe something that handles those triggers is using the memory.

by Tom Goddard, 10 months ago

Attachment:	memleak_test.py added

Python to select and unselect 5000 times without using ChimeraX command parsing.

comment:18 by Tristan Croll, 10 months ago

Typo on my part, sorry - I've been working with 8qie (the ribosome structure) the whole time, not 8qje.

comment:19 by Tristan Croll, 10 months ago

Not sure what's different (other than having restarted my Windows laptop), but now most of the accumulated memory usage *is* being cleaned up when I delete the model. Guess the garbage collector was being unusually sluggish the other day (running it a few times, I see sometimes it takes a minute or so to take effect). Anyway, the bigger accumulation of memory I see when using the explicit sel #1;~sel #1 looks to be because this creates an Objects instance for each command, where the bare sel; ~sel doesn't. Problem is that each Objects instance adds a callback to the 'deleted' trigger handler of every model it references (https://github.com/RBVI/ChimeraX/blob/50711ef3166e159aeb2862bd785fae9f9413e437/src/bundles/core/src/objects.py#L66), meaning that it's kept alive as long as that model exists. So:

from chimerax.core.commands import run

m = run(session, 'open 8qie')[0]

len(m.triggers.trigger_handlers('deleted'))
Out[3]: 0

for _ in range(50):
    run(session, 'sel;~sel')
    

len(m.triggers.trigger_handlers('deleted'))
Out[5]: 0

for _ in range(50):
    run(session, 'sel #1;~sel #1')

len(m.triggers.trigger_handlers('deleted'))
Out[7]: 100

So the big "memory leak" numbers I was complaining about turn out to be not a *true* leak, but amount to a de facto one when a model is kept open through a long series of commands. Seems like this could be avoided with some weakref magic in the callback?

comment:20 by Tom Goddard, 10 months ago

I see you are right that Objects instance stick around way too long (after commands finish executing, until the models that were specified eventually get deleted) due to the delete model triggers that Objects registers. That code used to not listen to triggers and just removed deleted models when Objects.models was used. Eric changed it 6 years ago to use the delete model trigger instead for unknown reasons

https://github.com/RBVI/ChimeraX/commit/df3f8aacf54f394c7935cf4fcfb42be0c47a92e5

I'm not entirely convinced this is why your long ISOLDE session uses too much memory. It contributes something because there might have large arrays of atom and bond pointers in these undeleted Objects instances, depending on how ISOLDE uses them. Most commands do not use Objects instead the take Atoms, or other more specific types.

comment:21 by Tristan Croll, 10 months ago

Looks to me like this most likely is the problem with my ISOLDE sessions... watching in the shell what happens when I start and stop a simulation, it turns out that starting a simulation creates *three* Objects instances, and stopping creates another one. After a bit of tinkering:

def test_func(session, atoms):
  pass

from chimerax.core.commands import CmdDesc, register

from chimerax.atomic import AtomsArg

desc = CmdDesc(required=[('atoms',AtomsArg)])

register('leaktest', desc, test_cmd, logger=session.logger)

... then leaktest sel with some atoms selected adds a single callback to the model's 'deleted' trigger, but e.g. leaktest #1/A:23 adds three (addendum: looks like it's one Objects for each level of specificity: #1 generates one, #1/A generates two; #1/A:80 three and #1/A:80@CA four). When I built ISOLDE's ribbon toolbar I redid the underlying functions for all the relevant functions to run a command with the relevant explicit atomspec (e.g. the start button effectively does isolde sim start {concise_residue_spec(selected_atoms(session))}.

Looking at the size of these (using ISOLDE's isolde demo crystal_intro model) after doing a few pretty common ISOLDE tasks...

import inspect
m = session.isolde.selected_model
objects = [t.__self__ for t in m.triggers.trigger_handlers('deleted')]

for o in objects:
    print(f'{sum([len(a) for a in o._atoms])} atoms, {sum([len(b) for b in o._bonds])} bonds, and {sum([len(p) for p in o._pseudobonds])} pseudobonds, {len(o._cached_atoms)} cached atoms.')

3348 atoms, 3371 bonds, and 0 pseudobonds, 3348 cached atoms.
3348 atoms, 0 bonds, and 0 pseudobonds, 3348 cached atoms.
3348 atoms, 0 bonds, and 0 pseudobonds, 3348 cached atoms.
3348 atoms, 3371 bonds, and 0 pseudobonds, 3348 cached atoms.
3348 atoms, 3371 bonds, and 0 pseudobonds, 3348 cached atoms.
17 atoms, 0 bonds, and 0 pseudobonds, 17 cached atoms.
17 atoms, 0 bonds, and 0 pseudobonds, 17 cached atoms.
17 atoms, 16 bonds, and 0 pseudobonds, 17 cached atoms.
3348 atoms, 3371 bonds, and 0 pseudobonds, 3348 cached atoms.
3348 atoms, 3371 bonds, and 0 pseudobonds, 3348 cached atoms.
3348 atoms, 3371 bonds, and 0 pseudobonds, 3348 cached atoms.
3348 atoms, 0 bonds, and 0 pseudobonds, 3348 cached atoms.
3348 atoms, 3371 bonds, and 0 pseudobonds, 3348 cached atoms.
3348 atoms, 3371 bonds, and 0 pseudobonds, 3348 cached atoms.
15 atoms, 0 bonds, and 0 pseudobonds, 15 cached atoms.
15 atoms, 0 bonds, and 0 pseudobonds, 15 cached atoms.
15 atoms, 14 bonds, and 0 pseudobonds, 15 cached atoms.
3348 atoms, 3371 bonds, and 0 pseudobonds, 3348 cached atoms.
1 atoms, 0 bonds, and 0 pseudobonds, 1 cached atoms.
1 atoms, 0 bonds, and 0 pseudobonds, 1 cached atoms.
1 atoms, 0 bonds, and 0 pseudobonds, 1 cached atoms.
1 atoms, 0 bonds, and 0 pseudobonds, 1 cached atoms.
3348 atoms, 3371 bonds, and 0 pseudobonds, 3348 cached atoms.

... So every time I start a simulation I accumulate 1-3 Objects encompassing the selection used to start the simulation, every time I stop a simulation I add another encompassing the entire model, and other little tasks accumulate smaller ones. For a big model that's going to add up fast.

comment:22 by Tristan Croll, 10 months ago

Perhaps not the most elegant possible solution, but this clears up the "big" memory accumulation issue for me. In objects.py:

def _model_deleted_cb_factory(model, obs):
    import weakref
    def _model_deleted_cb(_trigger_name, model, obs=weakref.proxy(obs)):
        try:
            obs._models.discard(model)
            if model in obs._model_instances:
                del obs._model_instances[model]
            del obs._handlers[model]
        except ReferenceError:
            pass
        from .triggerset import DEREGISTER
        return DEREGISTER
    return _model_deleted_cb

... then replace every instance of m.triggers.add_handler('deleted', self._model_deleted_cb) with m.triggers.add_handler('deleted', _model_deleted_cb_factory(m, self)).

There's still the slower leak that Tom noted (~1.6 GB lost apparently permanently after 500 rounds of sel #1;~sel #1 using 8qie), but that's a less pressing issue.

comment:23 by Tristan Croll, 10 months ago

Hmm... turns out the above *almost* works - except that "close {explicit atomspec}" no longer does anything. Looks like in that instance the Objects.__del__() method gets called *before* close() is executed (not sure how or why). If I comment out the last two lines:

    def __del__(self):
        for handler in self._handlers.values():
            handler.remove()
        self._handlers.clear()
#        self._model_instances.clear()
#        self._models.clear()

... then as far as I can tell so far everything behaves correctly.

comment:24 by Eric Pettersen, 10 months ago

On my machine using my own build, running:

open 8qje
perframe "sel ; ~sel" frames 5000

only increases memory use from 425MB to 555MB, and if run in nogui mode from 110MB to 114MB!

comment:25 by Eric Pettersen, 10 months ago

In the 1.9 release, it went from 435MB to 480MB. (BTW, in nogui mode in the comment above, also have to do a "wait 5000")

comment:26 by Eric Pettersen, 10 months ago

If I comment out the add_handler calls in core/objects.py, it goes from 568MB (why bigger?) to 587MB, so a definte improvement. I think I'll try to get one of the bigger leaks you guys were getting before making any changes.

comment:27 by Eric Pettersen, 10 months ago

Adding the explicit "#1" in the sel/~sel loop is the trick, memory usage going from 579MB to 4.35GB. Closing the model only drops it to 3.8GB though.

comment:28 by Eric Pettersen, 10 months ago

Commenting out the add_handler calls had a pretty major effect: 575MB→440MB (not sure what's going on there, but whatever). So since Objects instances should in general should have much shorter lifetimes than models, I'm going to revert to the former behavior of not using triggers and clearing out dead models on demand.

comment:29 by Eric Pettersen, 10 months ago

Resolution:	→ fixed
Status:	assigned → closed

Reverted to the older non-trigger/handler version of the code.

Fix: https://github.com/RBVI/ChimeraX/commit/b68a7975602e5e31c2565d4b8031f7a5af947045

Note: See TracTickets for help on using tickets.

Download in other formats: