[Chimera-users] Interactive Protein Structure and Sequence Alignment?

[Elaine Meng]

On Oct 13, 2015, at 6:44 PM, Abba Leffler <aleffler at alumni.princeton.edu> wrote:

> Dear Professor Meng,
> I'm a frequent user of Chimera, mostly for visualization of homology models of large complexes. There's one feature I've search for in Chimera and not found. I wonder if you can help me.
> 
> I would like to do two things, which are related.
> 
> First, I would like to be able to visualize where inserts, deletions, and mutations are on the template structure relative to the target sequence. Is there any way to do that? I haven't found one.
> 
> In a related question, I'd like to be able to interactively edit the sequence alignment (i.e. move indels that are in secondary structure elements) and then recompute the homology model to see if the DOPE score gets better or worse. Is that a possibility?
> 
> I've found that many people have told me that alignments have to be "manually corrected", but there don't seem to be many tools out there for doing that in a sane way. If there are any you could recommend, I would sincerely appreciate it.
> 
> All best,
> -Abba

Dear Abba,

(1) Any time you have a structure open in Chimera and associated with some sequence in MultAlign Viewer (Chimera’s sequence viewer), you can easily  map between the sequence and structure.  It can be an individual sequence or one within a multiple sequence alignment. You can just highlight an area of interest on the sequence with the mouse and it will be highlighted on the structure.  

See the Sequences and Structures tutorial:
<http://www.rbvi.ucsf.edu/chimera/docs/UsersGuide/tutorials/super.html>

… and/or the Multalign Viewer documentation, especially the part about sequence-structure association:
<http://www.rbvi.ucsf.edu/chimera/docs/ContributedSoftware/multalignviewer/framemav.html>
<http://www.rbvi.ucsf.edu/chimera/docs/ContributedSoftware/multalignviewer/multalignviewer.html#association>

If you used the Modeller interface in Chimera, you already have the target-template sequence alignment open in Chimera.  Then you could just use the mouse to highlight where in the sequence there is a mutation or insertion to have it highlighted on the structure(s).  Actually this does selection.  Then you can use the Actions menu to do something (e.g. coloring) to the current structure selection.  While you can’t highlight something in the sequence that isn’t there (a deletion), you could certainly highlight the positions around it.

(2) Multalign Viewer does allow for some small amount of manual editing, but it is not optimized for this purpose and other programs should be more suitable for any serious amount of editing.  However, I don’t do this myself so I cannot advise... maybe JalView?  Here are the instructions for manual editing in Multalign Viewer:
<http://www.rbvi.ucsf.edu/chimera/docs/ContributedSoftware/multalignviewer/multalignviewer.html#editing>

I hope this helps.  I’ve CC’d this reply to chimera-users, which is the address we recommend for asking Chimera questions. Best,
Elaine
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Elaine C. Meng, Ph.D.                       
UCSF Computer Graphics Lab (Chimera team) and Babbitt Lab
Department of Pharmaceutical Chemistry
University of California, San Francisco