<div dir="ltr"><span style="font-family:arial,sans-serif;font-size:12.666666984558105px">Elaine,</span><br><div><br></div><div><span style="font-family:arial,sans-serif;font-size:12.666666984558105px">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. </span></div><div><span style="font-family:arial,sans-serif;font-size:12.666666984558105px"><br></span></div><div><span style="font-family:arial,sans-serif;font-size:12.666666984558105px">Thanks for help,</span></div><div><span style="font-family:arial,sans-serif;font-size:12.666666984558105px"><br></span></div><div><span style="font-family:arial,sans-serif;font-size:12.666666984558105px">James</span></div></div><div class="gmail_extra"><br><br><div class="gmail_quote">2014-09-04 11:14 GMT+04:00 James Starlight <span dir="ltr"><<a href="mailto:jmsstarlight@gmail.com" target="_blank">jmsstarlight@gmail.com</a>></span>:<br><blockquote class="gmail_quote" style="margin:0 0 0 .8ex;border-left:1px #ccc solid;padding-left:1ex"><div dir="ltr"><div><div><div>Elaine, thank you very much!<br><br></div>I'll try to check literature.<br><br></div>Best,<br><br></div>James<br></div><div class="HOEnZb"><div class="h5"><div class="gmail_extra"><br><br><div class="gmail_quote">2014-09-03 19:36 GMT+02:00 Elaine Meng <span dir="ltr"><<a href="mailto:meng@cgl.ucsf.edu" target="_blank">meng@cgl.ucsf.edu</a>></span>:<br>
<blockquote class="gmail_quote" style="margin:0 0 0 .8ex;border-left:1px #ccc solid;padding-left:1ex">Hi James,<br>
I’m glad you found a solution for the technical problem.<br>
<br>
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.<br>
<br>
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!<br>
<br>
Best,<br>
<div>Elaine<br>
-----<br>
Elaine C. Meng, Ph.D.<br>
UCSF Computer Graphics Lab (Chimera team) and Babbitt Lab<br>
Department of Pharmaceutical Chemistry<br>
University of California, San Francisco<br>
<br>
</div><div><div>On Sep 3, 2014, at 5:11 AM, James Starlight <<a href="mailto:jmsstarlight@gmail.com" target="_blank">jmsstarlight@gmail.com</a>> wrote:<br>
<br>
> Thank you very much for suggestions!<br>
> Regarding techniqal question: Indeed I've found that the JalView + Chimera Mutalign give me best results! ;)<br>
><br>
> 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.<br>
><br>
> Kind regards,<br>
><br>
> James<br>
><br>
<br>
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