[Chimera-users] Analysis of the multiple alignments + structures

James Starlight jmsstarlight at gmail.com
Thu Sep 4 23:39:48 PDT 2014


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,


2014-09-04 11:14 GMT+04:00 James Starlight <jmsstarlight at gmail.com>:

> Elaine, thank you very much!
> I'll try to check literature.
> Best,
> James
> 2014-09-03 19:36 GMT+02:00 Elaine Meng <meng at cgl.ucsf.edu>:
>> Hi James,
>> I’m glad you found a solution for the technical problem.
>> I’m not really offering general research consulting on this list, and
>> don’t claim to be an expert whose opinions should be followed.  That said,
>> my general opinion is that evolutionary trace can offer additional insights
>> to just looking at the conservation in the columns of one big alignment.
>> Potential downsides are that for evolutionary trace you need a reliable
>> phylogenetic tree, and to be careful about the range and balance of the
>> data set of sequences.  In other words, tracing evolution is more difficult
>> than just aligning the sequences, but then you can see correlations of
>> specific mutations with evolutionary divergences.
>> Rather than asking me, better to look in the literature.  I realize that
>> is a daunting task, as there are many papers in this general area.  The
>> Lichtarge group is continuing to explore evolutionary trace, and many other
>> groups are using similar approaches.  My main involvement in the 2004
>> Madabushi et al. paper was to compile the list of experimentally evaluated
>> GPCR mutations and their literature references!
>> 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 3, 2014, at 5:11 AM, James Starlight <jmsstarlight at gmail.com>
>> wrote:
>> > Thank you very much for suggestions!
>> > Regarding techniqal question: Indeed I've found that the JalView +
>> Chimera Mutalign give me best results! ;)
>> >
>> > Elaine, how do you think might the *selective* analysis of the
>> alignments of *different* branches of the phylogenetic tree of the
>> olfactory receptors be more effective for the the prediction of the
>> mutations affecting its specifity and affinity towards different clases of
>> ligands (odors)? I've noticed that the same aproach have been used in your
>> 2003 study (Evolutionary trace of GPCRs) where you made conclusions (mainly
>> based on the  selectivy analys of the Opsins) about mutations affecting i)
>> ligand binding site, iii) constitutive activity as well as ii) coupling to
>> the G-protein.
>> >
>> > Kind regards,
>> >
>> > James
>> >
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