[Chimera-users] modeling selected protein mutations to a sequence

[Elaine Meng]

Hi Teresa,
Welcome to Chimera!  Although it does not predict 3D structure from amino acid sequence only, see part (B) below.

(A) If you already have a 3D structure such as a PDB file, in Chimera you can "mutate" an amino acid side chain from one type of residue to another.  However, it is only replacing the side chain and does not predict any other changes that might occur in the backbone or the rest of the structure.  It is a first-order simplistic approach that can suggest whether the new side chain fits into or clashes with the rest of the structure, or whether it might form H-bonds.

This virtual mutation of individual amino acid sidechains can be done with either the "swapaa" command or the Rotamers tool (in menu under Tools... Structure Editing):
<http://www.rbvi.ucsf.edu/chimera/docs/UsersGuide/midas/swapaa.html>
<http://www.rbvi.ucsf.edu/chimera/docs/ContributedSoftware/rotamers/framerot.html>

There's an example of using Rotamers in the "Structure analysis and comparison" tutorial:
<http://www.rbvi.ucsf.edu/chimera/docs/UsersGuide/tutorials/squalene.html>

(B) if you have an entire protein sequence for which you want to predict a structure, in Chimera you may be able to use the Modeller web service.  However, to use it would need to have two things: (1) a related 3D structure to use as "template" for comparative modeling, and (2) a sequence alignment that includes both your sequence (the "target") and the sequence of the template structure. 
<http://www.rbvi.ucsf.edu/chimera/docs/ContributedSoftware/multalignviewer/modeller.html#comparative> 

Some possible ways to get these necessary inputs are described here, with links to related tools:
<http://www.rbvi.ucsf.edu/chimera/docs/ContributedSoftware/multalignviewer/multalignviewer.html#approaches>

For example, you could enter your sequence in the Blast PDB tool to find related structures and also give you an alignment of the two sequences.

However, there are lots of other programs and web services (not connected to Chimera) for protein structure prediction, so you may want to search the web and/or literature to get a better idea of what is available.  It is also common to use some other program to predict the structure, and then open the resulting PDB file in Chimera for further analysis.  If there aren't any 3D structures related to your sequence, then you would have to use a de novo modeling program, as opposed to the comparative (homology) modeling described in (B).

I hope this helps,
Elaine
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Elaine C. Meng, Ph.D.                       
UCSF Chimera(X) team
Department of Pharmaceutical Chemistry
University of California, San Francisco

> On Apr 2, 2020, at 1:37 PM, Teresa Brito-Robinson <Teresa.Brito-Robinson.2 at nd.edu> wrote:
> 
> Hi Chimera users,
> I am trying chimera for the first time and my question is:
> 
> 	• How can I change (substitute) specific amino acids within an uploaded protein sequence to mimic a missense mutation?
> 
> 	• Or how can I enter a whole new custom made protein sequence into chimera, so I can probe different variants of a protein sequence.
> I don't know how to make the file like pdb (protein database) so I can fetch my custom sequence?
> 
> Thanks!
> Teresa