[Chimera-users] Difference in alignment of cofactor between Chimera and ChimeraX

[Elaine Meng]

Hello Derek,
You're welcome!

Thought I should also mention that in matchmaker you can specify more than one pair of chains, i.e. use multiple pairs of chains for the fit.  Which way is better depends on what you are trying to achieve: overall superposition of whole complex, or best fit of a single pair of chains.

This multichain fit can be done in either Chimera or ChimeraX with a matchmaker command option.  I'll use ChimeraX commands to illustrate:

open 3u7q
open 5n6y
hide 
ribbon

The ChimeraX log shows that 3u7q has four chains, two alpha (A,C) and two beta (B,D) whereas 5n6y has 6 chains, two alpha (A,D), two beta (B,E) and two delta (C,F).  So perhaps you want to use all of the alpha and beta chains from the structures for the fit instead of only A with A.

Now the trick is to figure out which alpha goes with which alpha and which beta with which beta.  I might be lazy and first just try ABCD in 3u7q as pairing with ABDE in 5n6y and see if that looks right.  I might also use coloring by polymer (figures out a color based on chain sequence) to make it clearer what's what.

color bypolymer
mm #2/A,B,D,E to #1/A,B,C,D pair ss

<http://rbvi.ucsf.edu/chimerax/docs/user/commands/matchmaker.html>

.... which actually looks right.  The alphas and betas are colored the same within a given PDB structure but different between the structures, probably because of small sequence differences (something like one structure has a couple more residues on one end or the other; I didn't investigate, but it's expected).  The Log reports:

RMSD between 1026 pruned atom pairs is 1.314 angstroms; (across all 1783 pairs: 3.281)

...now to check the placement of cofactors:

show ligand
~ribbon

You can see a more symmetrical fit, with similar displacements on both sides.

I hope this helps,
Elaine


> On Jul 7, 2020, at 9:39 AM, Derek Harris <derek.harris at aggiemail.usu.edu> wrote:
> 
> Hello Elaine,
> 
> Thank you very much for the rapid response. Following your commands, and seeing all the ligands, I now see what's happening. Just as you said; the proteins are each composed of two identical catalytic halves. In one half there is a nice alignment of the cofactors, but in the other half there is not. I was isolating, and only viewing, the chain where there isn't good alignment.
> 
> Thanks again!
> 
> Derek Harris
> Postdoctoral Fellow
> Seefeldt Lab
> Department of Chemistry and Biochemistry
> Utah State University
> 
> 
> On Tue, Jul 7, 2020 at 9:35 AM Elaine Meng <meng at cgl.ucsf.edu> wrote:
> Hello Derek,
> It does not make sense for the cofactor alignment to be different if the protein alignment is the same, because the cofactors are just moved rigidly along with their proteins. Also the results should be identical between Chimera and ChimeraX, assuming you are using the same options.
> 
> I get exactly the same alignment between these two proteins in the Chimera vs. ChimeraX.
> 
> Chimera commands (including display ligand only):
> open 3u7q
> open 5n6y
> mm #0 #1
> ~ribbon
> show ligand
> 
> ChimeraX commands:
> open 3u7q
> open 5n6y
> mm #2 to #1
> ~ribbon
> hide
> show ligand
> 
> In both programs, I get the same RMSD message to the Log:
> 
> RMSD between 375 pruned atom pairs is 0.968 angstroms; (across all 450 pairs: 2.998)
> 
> In both programs, matchmaker ends up choosing to align chain A to chain A.  Thus the cofactors in chains A are better superimposed than the ones in the other chains.
> 
> I hope this helps,
> Elaine
> -----
> Elaine C. Meng, Ph.D.                       
> UCSF Chimera(X) team
> Department of Pharmaceutical Chemistry
> University of California, San Francisco
> 
> > On Jul 6, 2020, at 6:47 PM, Derek Harris <derek.harris at aggiemail.usu.edu> wrote:
> > 
> > Hello,
> > 
> > I am trying to reproduce an alignment I had previously done in Chimera in ChimeraX with matchmaker command.
> > 
> > The protein alignment between the two programs is the same, but in ChimeraX the active-site cofactor of the matchstruct isn't aligning appropriately to the refstruct cofactor and is unreasonably placed in relation to even its own protein. In Chimera the two cofactors align nicely.
> > 
> > The two structures I am trying to align are 3U7Q and 5N6Y.
> > 
> > Thanks in advance for any assistance you can offer!
> > 
> > Derek Harris
> > Postdoctoral Fellow
> > Seefeldt Lab
> > Department of Chemistry and Biochemistry
> > Utah State University
> 
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