[Chimera-users] sequence & structure in Chimera

[Elaine Meng]

Hi Abhijit,
If I understand correctly, there were two questions here:

> One more question is it possible to take a protein sequence of a gene,  
> part of which is cloned, crystallized and 3d structure is available,  
> and superimposes the protein sequence with the reported crystal  
> structure? Or how can you model a protein sequence to generate a  
> putative structure, for the part that hasn’t been crystallized so far,

In Chimera,
(1) can you associate a structure with a sequence that is read in from  
a separate file?
   short answer: yes, if that sequence is in an alignment
(2) can you do comparative modeling (create a 3D model of an unknown  
structure starting from a known structure that is thought to be  
similar)?
   short answer: no, except simplistic replacement of a few side chains  
with the command "swapaa"

I'll start with #2: Chimera does not do comparative modeling or  
threading different sequences on a known structure.  Besides the  
approaches mentioned by Eric (getting a model from MODBASE or using the  
MODELLER program to make the model yourself), listed below are several  
web servers that might be useful. I believe the first two replace side  
chains while the others perform more complete modeling (can handle  
insertions/deletions and adjust the backbone).  It's been a while since  
I used any of these, however, so you should read any author-provided  
information.

- SCWRL server
http://www1.jcsg.org/scripts/prod/scwrl/serve.cgi
- Maxsprout server
http://www.ebi.ac.uk/maxsprout/
- ModWeb server (requires registration)
http://alto.compbio.ucsf.edu/modweb-cgi/main.cgi
- RAPPER server (registration encouraged)
http://mordred.bioc.cam.ac.uk/~rapper/
- PSIPRED server
http://bioinf.cs.ucl.ac.uk/psipred/
- Swiss-Model server
http://swissmodel.expasy.org//SWISS-MODEL.html

Now question #1.  You already saw the Sequence tool, which shows the  
exact sequence of any peptide or nucleotide chains in structures open  
in Chimera.  However, you might want to read in a sequence from a  
separate file and associate it with the structure to allow the same  
kinds of crosstalk (a selection on the sequence selects the structure  
and vice versa).  You can do that, if you have an alignment of that  
sequence with one or more additional sequences.  These other sequences  
don't need to have any structures, and your sequence of interest does  
not have to match the structure exactly to associate with it (often  
there are point mutations, or the sequence is for a close homolog of  
the structure, or the structure is missing a few residues here and  
there, or is only one domain from the whole sequence).

Here's a list of the sequence alignment formats that can be read (you  
can just use File... Open in the Chimera menu):
http://www.cgl.ucsf.edu/chimera/docs/UsersGuide/filetypes.html#alignment

and the "Sequence-Structure Association" section in this page may be  
useful:
http://www.cgl.ucsf.edu/chimera/docs/ContributedSoftware/ 
multalignviewer/framemav.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