[chimera-dev] Using Chimera to display family shuffling information.

[Elaine Meng]

On Apr 8, 2015, at 5:11 PM, Matthew Tiffany <matt.tiffany at icloud.com> wrote:

> To Whom It May Concern:
> I am interested in displaying results from DNA shuffling experiments on a crystal structure. Here is a graphical tool that I have found to do this: http://qpmf.rx.umaryland.edu/XoverDemo.html
> 
> What I would like to do is input an alignment of parental sequences and separately a chimeric protein that is derived from the parental sequences by domain shuffling. Then color code a related structure based upon which domain of a parent the chimeric protein came from. The Xover program does this in a graph, but I would like to be able to do this in 3D space. It is similar to color coding by conservation in MultiAlign, but not exactly. Is there any existing plugin that you may be aware of that does this already or a potential backbone plugin that I can use as a starting point to try and code it myself.
> 
> Regards,
> Matthew Tiffany
> Postdoctoral Fellow
> Mark A. Kay Laboratory
> Stanford University

Hi Matthew,
I’ve CC’d the chimera-users list since my answer doesn’t involve programming...

Chimera itself includes a lot of sequence-structure interactivity and related features.  Certainly you could do it semi-manually:

(1) open your 3D structure and sequence alignment in Chimera. You can just the “File… Open” dailog.  Chimera understands several sequence alignment formats. 
<http://www.rbvi.ucsf.edu/chimera/docs/UsersGuide/filetypes.html#alignment>
<http://www.rbvi.ucsf.edu/chimera/docs/ContributedSoftware/multalignviewer/framemav.html>

(2) associate the structure with a sequence in the alignment.  I don’t know exactly what your data look like, and so this requires some judgment calls and deciding amongst different strategies.  My thought is at least initially, don’t worry about which sequence is associated with the structure, just try to get it associated with any sequence so that the 3D mapping along the alignment as a whole is correct.
— approach A: just use sequence window menu Structure… Associations to force association with any one of the sequences, if it didn’t already associate automatically
— approach B: add the sequence of the chimeric protein to your sequence alignment, sequence window menu Edit… Add Sequence, use From Structure (if it adds it poorly you may have to go through a few cycles of Edit… Delete Sequences/Gaps to remove it and then adding it back with different alignment parameters)
… I’m leaning toward approach B as the better approach, but you can see whether one or the other works better for your situation…
<http://www.rbvi.ucsf.edu/chimera/docs/ContributedSoftware/multalignviewer/multalignviewer.html#association>

(3) then you can select the different parts of the structure for coloring by using the mouse in the sequence window to select the appropriate ranges of residues in the structure-associated sequence
<http://www.rbvi.ucsf.edu/chimera/docs/ContributedSoftware/multalignviewer/multalignviewer.html#regions>

Another approach to #1-2 above would be to start with a sequence of just your structure (for example, open the structure, use Favorites… Sequence to show its sequence) and Blast against the PDB, then load in the Blast alignment.  However, you already have your own alignment so I don’t think it would get you much further.  Further, there is a newish “mda” command that  performs multiple steps including blasting against PDB, automatically loading in the structures and Blast alignment, and conveniently laying out the structure hits N->C (based on alignment to query) in the 3D display.  This also wouldn’t get you much further toward the color mapping of your chimeric structure, but the layout stuff is cool.  It might not work if your shuffled cassettes are pretty short though. 
<http://www.rbvi.ucsf.edu/chimera/docs/UsersGuide/midas/mda.html>

I hope this helps,
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