[Chimera-users] New to the board

[Elaine Meng]

Hi Pat,
Welcome!
The answer includes many yeses but a significant sticking point.   
Chimera does not do homology modeling or predict changes in a  
structure resulting from mutation.   You can change residues from one  
type to another, but there is no attempt to put the new side chains  
in energetically favorable positions.  We are working on adding  
rotamer information, which would then allow one to choose reasonable  
conformations for the sidechains, but that is (a) still in progress,  
not available, and (b) would not change the backbone at all.  You can  
do energy minimization, but minimization (in any program) should  
never be viewed as a structure prediction tool; it will only find  
conformations very close to the starting point.  I would probably  
seek a different program to model the coordinates of the mutated  
structure, even though all the steps you asked about can be done in  
Chimera...

With those caveats in mind, here are the specific answers:

> a. It is possible to change part of the sequence on the chain (from  
> AAAA to EEEE for instance).

Yes, you can use the "swapaa" command:
http://www.cgl.ucsf.edu/chimera/docs/UsersGuide/midas/swapaa.html

See also bond rotation and clash detection:
http://www.cgl.ucsf.edu/chimera/docs/ContributedSoftware/ 
structuremeas/structuremeas.html#adjust
http://www.cgl.ucsf.edu/chimera/docs/ContributedSoftware/findclash/ 
findclash.html

> b. Is it possible to then use the changed sequence (B) to morph it  
> against the original 3d sequence (A)

Yes, you can use Morph Conformations to transition between different  
conformations of the same structure or between different but related  
structures:
http://www.cgl.ucsf.edu/chimera/docs/ContributedSoftware/morph/ 
morph.html

> c. Is it possible to align the changed fragment of B with the  
> original A

Yes, in fact you should align the structures before morphing, if they  
aren't already.  There are many different ways to align structures  
(MatchMaker tool, matchmaker command, match command):
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

See also the "Matching Structures" section of the "Images for  
Publication" tutorial for examples:
http://www.cgl.ucsf.edu/chimera/docs/UsersGuide/tutorials/ 
frameimages.html

> d. Could the changed sequence (B) be saved for future use or does  
> one have to go through the process of creating it each time it is  
> used on CHIMERA?
>
Yes, you can save the new structure by writing it out to a PDB file,  
or by saving a Chimera session:
http://www.cgl.ucsf.edu/chimera/docs/UsersGuide/savemodel.html
http://www.cgl.ucsf.edu/chimera/docs/UsersGuide/sessions.html

> thanks much
> pat
>
You're welcome - and I hope I haven't deterred you from using Chimera  
in general, for steps other than structure prediction/modeling.  Best,
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