Opened 3 years ago

Last modified 3 years ago

#8559 assigned enhancement

Difficult morphing scenario

Reported by: Tristan Croll Owned by: Tom Goddard
Priority: normal Milestone:
Component: Structure Comparison Version:
Keywords: Cc: Elaine Meng
Blocked By: Blocking:
Notify when closed: Platform: all
Project: ChimeraX

Description 

The following bug report has been submitted:
Platform:        Windows-10-10.0.22621
ChimeraX Version: 1.6.dev202212302205 (2022-12-30 22:05:38 UTC)
Description
Not a bug as such, but it struck me that this pair of models would make an interesting challenge case if you're ever planning on playing with new morphing algorithms. They're the LRP2 dimer captured in the extracellular (pH 7.5) and intracellular (pH 5.2) states - the conformational change is just *staggeringly* large and complex - like a pair of pythons uncoiling and recoiling around each other. In my hands at least the existing morph algorithm just rips it apart.

OpenGL version: 3.3.0 NVIDIA 528.24
OpenGL renderer: NVIDIA GeForce RTX 3070 Laptop GPU/PCIe/SSE2
OpenGL vendor: NVIDIA Corporation

Python: 3.9.11
Locale: en_GB.cp1252
Qt version: PyQt6 6.4.0, Qt 6.4.0
Qt runtime version: 6.4.1
Qt platform: windows

Manufacturer: HP
Model: HP ZBook Studio 15.6 inch G8 Mobile Workstation PC
OS: Microsoft Windows 11 Pro (Build 22621)
Memory: 34,007,068,672
MaxProcessMemory: 137,438,953,344
CPU: 16 11th Gen Intel(R) Core(TM) i7-11800H @ 2.30GHz
OSLanguage: en-GB

Installed Packages:
    alabaster: 0.7.12
    appdirs: 1.4.4
    asttokens: 2.2.1
    Babel: 2.11.0
    backcall: 0.2.0
    blockdiag: 3.0.0
    build: 0.8.0
    certifi: 2022.12.7
    cftime: 1.6.2
    charset-normalizer: 2.1.1
    ChimeraX-AddCharge: 1.5.8
    ChimeraX-AddH: 2.2.3
    ChimeraX-AlignmentAlgorithms: 2.0
    ChimeraX-AlignmentHdrs: 3.3.1
    ChimeraX-AlignmentMatrices: 2.1
    ChimeraX-Alignments: 2.8
    ChimeraX-AlphaFold: 1.0
    ChimeraX-AltlocExplorer: 1.0.3
    ChimeraX-AmberInfo: 1.0
    ChimeraX-Arrays: 1.0
    ChimeraX-Atomic: 1.43.4
    ChimeraX-AtomicLibrary: 10.0
    ChimeraX-AtomSearch: 2.0.1
    ChimeraX-AxesPlanes: 2.3
    ChimeraX-BasicActions: 1.1.2
    ChimeraX-BILD: 1.0
    ChimeraX-BlastProtein: 2.1.2
    ChimeraX-BondRot: 2.0.1
    ChimeraX-BugReporter: 1.0.1
    ChimeraX-BuildStructure: 2.7.2
    ChimeraX-Bumps: 1.0
    ChimeraX-BundleBuilder: 1.2
    ChimeraX-ButtonPanel: 1.0.1
    ChimeraX-CageBuilder: 1.0.1
    ChimeraX-CellPack: 1.0
    ChimeraX-Centroids: 1.3.1
    ChimeraX-ChangeChains: 1.0.2
    ChimeraX-CheckWaters: 1.3.1
    ChimeraX-ChemGroup: 2.0
    ChimeraX-Clashes: 2.2.4
    ChimeraX-Clipper: 0.20.0
    ChimeraX-ColorActions: 1.0.3
    ChimeraX-ColorGlobe: 1.0
    ChimeraX-ColorKey: 1.5.2
    ChimeraX-CommandLine: 1.2.5
    ChimeraX-ConnectStructure: 2.0.1
    ChimeraX-Contacts: 1.0.1
    ChimeraX-Core: 1.6.dev202212302205
    ChimeraX-CoreFormats: 1.1
    ChimeraX-coulombic: 1.4.1
    ChimeraX-Crosslinks: 1.0
    ChimeraX-Crystal: 1.0
    ChimeraX-CrystalContacts: 1.0.1
    ChimeraX-DataFormats: 1.2.3
    ChimeraX-Dicom: 1.1
    ChimeraX-DistMonitor: 1.3
    ChimeraX-DockPrep: 1.1
    ChimeraX-Dssp: 2.0
    ChimeraX-EMDB-SFF: 1.0
    ChimeraX-ESMFold: 1.0
    ChimeraX-ExperimentalCommands: 1.0
    ChimeraX-FileHistory: 1.0.1
    ChimeraX-FunctionKey: 1.0.1
    ChimeraX-Geometry: 1.2
    ChimeraX-gltf: 1.0
    ChimeraX-Graphics: 1.1
    ChimeraX-Hbonds: 2.4
    ChimeraX-Help: 1.2.1
    ChimeraX-HKCage: 1.3
    ChimeraX-IHM: 1.1
    ChimeraX-ImageFormats: 1.2
    ChimeraX-IMOD: 1.0
    ChimeraX-IO: 1.0.1
    ChimeraX-ISOLDE: 1.6.dev0
    ChimeraX-ItemsInspection: 1.0.1
    ChimeraX-Label: 1.1.7
    ChimeraX-ListInfo: 1.1.1
    ChimeraX-Log: 1.1.5
    ChimeraX-LookingGlass: 1.1
    ChimeraX-Maestro: 1.8.2
    ChimeraX-Map: 1.1.3
    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: 1.0.1
    ChimeraX-MatchMaker: 2.0.11
    ChimeraX-MDcrds: 2.6
    ChimeraX-MedicalToolbar: 1.0.2
    ChimeraX-Meeting: 1.0.1
    ChimeraX-MLP: 1.1
    ChimeraX-mmCIF: 2.10
    ChimeraX-MMTF: 2.2
    ChimeraX-Modeller: 1.5.8
    ChimeraX-ModelPanel: 1.3.6
    ChimeraX-ModelSeries: 1.0.1
    ChimeraX-Mol2: 2.0
    ChimeraX-Mole: 1.0
    ChimeraX-Morph: 1.0.1
    ChimeraX-MouseModes: 1.2
    ChimeraX-Movie: 1.0
    ChimeraX-Neuron: 1.0
    ChimeraX-Nucleotides: 2.0.3
    ChimeraX-OpenCommand: 1.9.3
    ChimeraX-PDB: 2.6.10
    ChimeraX-PDBBio: 1.0
    ChimeraX-PDBLibrary: 1.0.2
    ChimeraX-PDBMatrices: 1.0
    ChimeraX-PickBlobs: 1.0.1
    ChimeraX-Positions: 1.0
    ChimeraX-PresetMgr: 1.1
    ChimeraX-PubChem: 2.1
    ChimeraX-ReadPbonds: 1.0.1
    ChimeraX-Registration: 1.1.1
    ChimeraX-RemoteControl: 1.0
    ChimeraX-RenderByAttr: 1.0
    ChimeraX-RenumberResidues: 1.1
    ChimeraX-ResidueFit: 1.0.1
    ChimeraX-RestServer: 1.1
    ChimeraX-RNALayout: 1.0
    ChimeraX-RotamerLibMgr: 3.0
    ChimeraX-RotamerLibsDunbrack: 2.0
    ChimeraX-RotamerLibsDynameomics: 2.0
    ChimeraX-RotamerLibsRichardson: 2.0
    ChimeraX-SaveCommand: 1.5.1
    ChimeraX-SchemeMgr: 1.0
    ChimeraX-SDF: 2.0.1
    ChimeraX-Segger: 1.0
    ChimeraX-Segment: 1.0
    ChimeraX-SelInspector: 1.0
    ChimeraX-SeqView: 2.8.1
    ChimeraX-Shape: 1.0.1
    ChimeraX-Shell: 1.0.1
    ChimeraX-Shortcuts: 1.1.1
    ChimeraX-ShowSequences: 1.0.1
    ChimeraX-SideView: 1.0.1
    ChimeraX-Smiles: 2.1
    ChimeraX-SmoothLines: 1.0
    ChimeraX-SpaceNavigator: 1.0
    ChimeraX-StdCommands: 1.10.1
    ChimeraX-STL: 1.0
    ChimeraX-Storm: 1.0
    ChimeraX-StructMeasure: 1.1.1
    ChimeraX-Struts: 1.0.1
    ChimeraX-Surface: 1.0
    ChimeraX-SwapAA: 2.0.1
    ChimeraX-SwapRes: 2.2
    ChimeraX-TapeMeasure: 1.0
    ChimeraX-Test: 1.0
    ChimeraX-Toolbar: 1.1.2
    ChimeraX-ToolshedUtils: 1.2.1
    ChimeraX-Topography: 1.0
    ChimeraX-Tug: 1.0.1
    ChimeraX-UI: 1.26
    ChimeraX-uniprot: 2.2.1
    ChimeraX-UnitCell: 1.0.1
    ChimeraX-ViewDockX: 1.1.6
    ChimeraX-VIPERdb: 1.0
    ChimeraX-Vive: 1.1
    ChimeraX-VolumeMenu: 1.0.1
    ChimeraX-VTK: 1.0
    ChimeraX-WavefrontOBJ: 1.0
    ChimeraX-WebCam: 1.0.1
    ChimeraX-WebServices: 1.1.1
    ChimeraX-Zone: 1.0.1
    colorama: 0.4.5
    comm: 0.1.2
    comtypes: 1.1.10
    contourpy: 1.0.6
    cxservices: 1.2
    cycler: 0.11.0
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    decorator: 5.1.1
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    entrypoints: 0.4
    executing: 1.2.0
    filelock: 3.7.1
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    funcparserlib: 1.0.1
    grako: 3.16.5
    h5py: 3.7.0
    html2text: 2020.1.16
    idna: 3.4
    ihm: 0.35
    imagecodecs: 2022.9.26
    imagesize: 1.4.1
    importlib-metadata: 6.0.0
    ipykernel: 6.19.2
    ipython: 8.7.0
    ipython-genutils: 0.2.0
    jedi: 0.18.2
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    nest-asyncio: 1.5.6
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    openvr: 1.23.701
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    ParmEd: 3.4.3
    parso: 0.8.3
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File attachment: 8em7_8em4_rebuilt.zip

8em7_8em4_rebuilt.zip​

Attachments (2)

8em7_8em4_rebuilt.zip​ (4.8 MB ) - added by Tristan Croll 3 years ago.
Added by email2trac
morph.mp4​ (4.8 MB ) - added by Tom Goddard 3 years ago.
Morph using "matchmaker #1 to #2 ; morph #1,​2" using attached rebuilt 8em4 and 8em7 pdb files.

Change History (6)

by Tristan Croll, 3 years ago

Attachment: 8em7_8em4_rebuilt.zip​ added

Added by email2trac

comment:1 by pett, 3 years ago

Component: Unassigned → Structure Comparison
Owner: set to Tom Goddard
Platform: → all
Project: → ChimeraX
Status: new → assigned
Summary: ChimeraX bug report submission → Difficult morphing scenario
Type: defect → enhancement

in reply to:  3 comment:2 by Tristan Croll, 3 years ago 

A caveat: based on low-resolution connectivity in the consensus map for
8em4 I concluded the authors had mis-assigned chain IDs for residues ~3115
through to the C-termini, and swapped them. They’ve since pointed me a map
derived from focused refinement of that region, which clearly shows they
had it right in the first place. Switching it back slightly reduces the
scale of the challenge, but not by much. :)

On Fri, 24 Feb 2023 at 18:18, ChimeraX <ChimeraX-bugs-admin@cgl.ucsf.edu>
wrote:

comment:3 by Tom Goddard, 3 years ago

Cc: Elaine Meng added

ChimeraX does make a comical morph of this dimer where each protein has 4500 residues. It fragments each protein into a dozen pieces that mostly move rigidly and crashes maybe 10000 atoms of one monomer through the other. Still it kind of achieves what is intended, to show how the two conformations differ. The algorithm was implemented by Conrad Huang 15-20 years ago in Chimera and carried over in ChimeraX and I believe is from the Yale Morph Server

The morph server: a standardized system for analyzing and visualizing macromolecular motions in a database framework.
WG Krebs, M Gerstein (2000). Nucleic Acids Res 28: 1665-75.

Would be good to add that citation to the docs. The method divides the proteins into semi-rigid pieces and rotates and translates those to their new locations while simultaneously adjusting all torsions to get backbones and sidechains from initial to final conformations. It has no idea of clashes or even about keeping the consecutive pieces close to each other.

Surely something better than this circa 2000 algorithm could be done. I'd estimate the current code has seen 3 months of full-time work. A fancier method might take 6 months of full-time work, too much for a summer intern. Would be interesting, but I don't think it is likely to happen given that we have so many other funded projects and that is not one of them. Maybe you (Tristan) want to hire someone to work on it?

by Tom Goddard, 3 years ago

Attachment: morph.mp4​ added

Morph using "matchmaker #1 to #2 ; morph #1,​2" using attached rebuilt 8em4 and 8em7 pdb files.

comment:4 by Tristan Croll, 3 years ago

Maybe you (Tristan) want to hire someone to work on it?

Sadly that's unlikely to happen. Recent situation at Altos is that going forward all new hires have to be justified according to their alignment with Altos' core mission. That sort of "general purpose tool development" just won't qualify - in fact, by the looks of it I might struggle to get support for anything more than the occasional intern to work on core ISOLDE functionality. Still scope for bigger things via collaborations, but it will all be a little more limited than I was originally led to believe. :(

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