Dear Chimera users! I've been interested in the possibility to make some sort of evolutional analysis in Chimera using MSA of the protein under study, its X-ray structures and its superimpositions as well as obtained projections of the sequence conservation in key (functionally-important) hot spots made by means of mutalign plugin. For my particular case I have MSA for the big number of olfactory receptors sequences (including receptors from different sub-groups associated with different specificity towards different odors). As the result I should to find possibility to sort these sequences of each ORs based on some phylogenetic study (I thinks to obtain tree-like view of the sequences) considering explicitly residues of the receptor's binding site. One of the possible idea is to keep only those residues of interest (from the ligand binding cavity) and rerun the alignment on these mini sequences to make prediction of new family of Or that may interact with the same kind of odorants. Would this idea is better realized by means of differential evolutional tracing method (because In fact we need to subtract conservative residues of one sub-branch of the whole phylogeny tree from those of all (root) OR) or there are any trivial alternatives? Thanks for help, James 2014-09-19 22:04 GMT+02:00 James Starlight <jmsstarlight@gmail.com>:

Dear Elaine,

thanks you very much for the suggestions! It's always a big pleasure to get advise from the experienced person :) BTW may be the next question will be more in connection with your present job (Chimera software developer). I wounder whether it *in principle* possible to find an academic post-doc job focused mainly on molecular visualization and animation (as the trivial example os such job in my mind is to make a pictures and movies of the proteins and it's complexes using data from different resolution's experimental techniques and modelling). How do you think will it be easily to obtain such job for the person who's PhD was based on structural biology (experimentalist) or alternatively focused on molecular modeling and bioinformatics ?

Kind regards,

Gleb

2014-09-16 23:36 GMT+04:00 Elaine Meng <meng@cgl.ucsf.edu>:

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Dear Gleb, I really don't know the answer! I've never searched for such a position myself. I could only guess that you would try to search for "teaching" in addition to the keywords about molecular modeling and structural bioinformatics.

For postdocs at least, most people are looking for research lab positions rather than teaching. In that case they identify research papers that describe the types of work that they want to do, then contact the labs of the authors about possible postdoc opportunities.

The only other idea I have is to try to figure out (by online searching) what institutions offer classes in chemistry and biology that include structures/modeling, then see if they have openings for instructors.

I'm sorry, I don't think these are very bright ideas, or anything that you wouldn't have thought of yourself already. Best, Elaine ---------- Elaine C. Meng, Ph.D. UCSF Computer Graphics Lab (Chimera team) and Babbitt Lab Department of Pharmaceutical Chemistry University of California, San Francisco

On Sep 16, 2014, at 12:09 PM, James Starlight <jmsstarlight@gmail.com> wrote:

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Hi Elaine,

thank you for the suggestions again! By that time I've noticed that to find structural bioinformatics position is much complicated than to find positions in fields of theoretical biophysics, computational biology or even genome bioinformatics. BTW according to your experience what keywords might be to seek position focused rather not to the research but to make some teaching practice, workshops and tutorials (focused on structural bioinformatics and modeling)?

Kind regards,

Gleb

2014-09-10 2:52 GMT+04:00 Elaine Meng <meng@cgl.ucsf.edu>: Glad it was useful! I don't know if there is a specific name other than "structural bioinformatics," but especially now that more and more structures are known (in combination with perhaps too many sequences!), it should be a fruitful and interesting area of research. Best, Elaine

On Sep 6, 2014, at 12:00 AM, James Starlight <jmsstarlight@gmail.com> wrote:

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Hi Elaine,

thank you very much It was really useful for me! I plan to look for the post-doc for myself on next year switching from the modeling and theoretical chemistry to structural bioinformatics coupled with the phylogenetic analysis (I don't know yet precise name of this discipline in the computational biology) so It will be very helpful!

All the best,

James

2014-09-05 20:59 GMT+04:00 Elaine Meng <meng@cgl.ucsf.edu>: HI James, Sorry, Chimera does not do evolutionary trace calculations. I would definitely have mentioned it if it did! In Chimera, if you input a tree along with your alignment, you can click a node on the tree and easily extract only the sequences for that node, but there is nothing to compare the residues from one set of sequences with those from another set of sequences, other than looking at the separate alignment windows yourself. Also, Chimera cannot create the tree, it must be read in from a file. < http://www.rbvi.ucsf.edu/chimera/docs/ContributedSoftware/multalignviewer/fr...

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… see the section on Trees: < http://www.rbvi.ucsf.edu/chimera/docs/ContributedSoftware/multalignviewer/mu...

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… example image of tree+alignment in Chimera: < http://www.rbvi.ucsf.edu/chimera/data/tutorials/systems/redoxin/ConSurf-1hd2...

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Although I’m still very interested in GPCRs, I have not actively

worked on them for >10 years, so I’m not the best person to ask for current information. I know there is a GPCRdb, but I don’t know if it has been kept up to date. You could try googling or pubmed-searching for “gpcr alignments” or similar terms.

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Two ideas for evolutionary trace:

(1) The Lichtarge group has an evolutionary trace server. <http://mammoth.bcm.tmc.edu/ETserver.html>

At first I thought you could only put in a PDB ID and not have any

control over what sequences are used (which might not be useful for your research), but then I noticed a “GPCRs” link on the left-hand side. Click that and it lets you choose specific GPCR subsets, which sounds exactly like the kind of calculation you wanted. I don’t know if it includes your specific groups of interest, however, and I don’t see a way to use your own alignments.

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<http://mammoth.bcm.tmc.edu/gpcr/diff_GPCRA.html>

(2) JEvTrace, a Java implementation of evolutionary trace. <http://compbio.berkeley.edu/people/marcin/jevtrace/>

I have one correction to that page. It says you can show results using the MSF Viewer tool in Chimera, which no longer exists. You can still use Chimera, just the Multalign Viewer tool instead (Multalign Viewer menu: "File… Load SCF/Seqsel File” will open the file from JEvTrace). I’ll email the author and tell him to update that information.

Those are all my ideas. If neither helps you, you may have to continue searching for programs or other tools and instructions on how to do the steps of the analysis yourself. I hope this helps, Elaine ----- Elaine C. Meng, Ph.D. UCSF Computer Graphics Lab (Chimera team) and Babbitt Lab Department of Pharmaceutical Chemistry University of California, San Francisco

On Sep 4, 2014, at 11:39 PM, James Starlight <jmsstarlight@gmail.com> wrote:

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Elaine,

onequestion about your 2003 GPCRs study: in this paper you've used the method called differential evolution tracing to detect functionally-relevant amino acids for rhodopsin only (substration of the conservative residues found in rhodopsin from those found in whole set of A-class GPCRs). I wounder if there any possibility for this method in Chimera's mutalign (in case where I have big alignment with thesequences of all olfactory receptors) to substract residues found in one philogenetic branch (corresponded to specified sub-class or group of those receptors) from the residues common to all olfactory receptors or (ii) substract residues common for the all olfactory receptors from those common to all A-class GPCRs? BTW do you know open-access data-bases consisted of the evolutional (alignments) information to the GPCRs? it's intresting to compare my alignment with some references.

Thanks for help,

James

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