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@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