[chimera-dev] Building a multimer model

[Elaine Meng]

Hi Benjamin,
There is probably more than one way to do this in Chimera, but I'd  
open the protein of interest six times and match it to the six  
monomers of the related protein. Let's call your protein "A" and the  
similar protein "B" (for which a hexamer is available or can be  
easily constructed from matrices in the PDB file).  Since you didn't  
mention the specifics, I didn't try the whole process outlined below  
(not having a good example to work with), but have used the tools in  
other contexts.

This is kind of a brute force approach.  Someone else may know of a  
more elegant way...

Making the hexamer of B:
If the PDB file doesn't already have a hexamer, it should have matrix  
information that allows it to be constructed.  If BIOMT, use  
Multiscale Models (under Tools... Higher-Order Structure).   
Initially, this doesn't copy all the atoms but just makes surfaces  
for computational expediency.  Since you will need copies of all the  
atoms for matching, using the Multiscale Models GUI: select "All"  
chains, change their style to anything other than surface (e.g.  
Show... Ribbons).  You can see the model IDs of the copies of B in  
the Model Panel (under Favorites).  If SMTRY, CRYST1, or MTRIX you  
could use the Unit Cell tool (under Tools... Higher-Order Structure)  
instead of Multiscale Models.  Relevant manual pages:
http://www.cgl.ucsf.edu/chimera/docs/ContributedSoftware/multiscale/ 
framemulti.html
http://www.cgl.ucsf.edu/chimera/docs/ContributedSoftware/unitcell/ 
unitcell.html

Matching the 6 copies of A to the monomers of B:
Options for matching are the "match" command or MatchMaker (GUI under  
Tools... Structure Comparison, also implemented as a command,  
"matchmaker").  If you wanted to name specific atoms to use for  
fitting, you'd use the "match" command.  That can be tedious, and I'd  
try MatchMaker first - if there is some sequence similarity, even  
fairly low, it usually works quite well.  By default, it iterates the  
fit so that only residues that match well in space are ultimately  
used to superimpose the proteins. That means the parts that are  
different should not interfere with a good fit of the parts that are  
the same.  You can adjust several parameters, but for example if B is  
model 0, chains A-F and copies of A are models 1-6, these commands  
would use the matchmaker defaults:
   matchmaker #0:.a #1 pair ss
   matchmaker #0:.b #2 pair ss
   matchmaker #0:.c #3 pair ss
   matchmaker #0:.d #4 pair ss
   matchmaker #0:.e #5 pair ss
   matchmaker #0:.f #6 pair ss
(pair ss just means to use the specified chains rather than trying  
all chain combinations between the models)  You could specify other  
parameters with various keywords, for example the stringency to use  
when iterating the fit, how much weight secondary structure should  
have vs. the residue types in the sequence, etc.  Relevant manual pages:
http://www.cgl.ucsf.edu/chimera/docs/ContributedSoftware/matchmaker/ 
matchmaker.html
http://www.cgl.ucsf.edu/chimera/docs/UsersGuide/midas/matchmaker.html
http://www.cgl.ucsf.edu/chimera/docs/UsersGuide/midas/match.html

I hope this helps,
Elaine
-----
Elaine C. Meng, Ph.D.                          meng at cgl.ucsf.edu
UCSF Computer Graphics Lab and Babbitt Lab
Department of Pharmaceutical Chemistry
University of California, San Francisco
                      http://www.cgl.ucsf.edu/home/meng/index.html




On Apr 5, 2007, at 12:10 AM, Benjamin G.S. Horsman wrote:

> Hello,
>
> My name is Benjamin Horsman and I am a student at the University of
> Toronto.  I have what should be a basic (possibly naive) question
> regarding protein modelling that I was hoping you might be able to
> answer for me or point my in the right direction.  I have been
> studying the structure of a bacterial protein complex, trying to
> understand how it interacts with several known binding partners.  The
> complex is known to be a hexameric homomultimer.  Recently the
> structure of the subunit protein was solved.  However, only the
> monomeric form of the protein was determined, and the corresponding
> PDB file does not contain coordinates for the multimer (i.e., no
> BIOMT1, BIOMT2, BIOMT3 matrix values).  I would like to assemble a
> model of the hexameric complex for visual inspection and for some
> docking studies.  What would be the best way to accomplish this?
>
> There are several structures in the PDB of hexameric protein complexes
> composed of subunits with very close structural alignment to my
> protein of interest, differing in two regions of the protein that are
> outside of the multimer binding regions.  I believe that my protein
> complex posses very similar or nearly identical geometry to these
> known complexes.  Is there any way to basically insert my protein into
> this geometry?  Can this be done in Chimera?  If not, is there any
> program or web server that allows this to be done?  Or are you aware
> of a better way to get this done?
>
> Thank you for your time.  Any help is greatly appreciated.
>
>
> Benjamin Horsman
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