Hi All,<br><br>In the figure illustrating the various tautomers, some are actually aromatic; wouldn't these be the predominant species at pH 7.4? Also, how could one start docking without a properly defined ligand?<br>
<br>Thanks in advance,<br>Nancy<br><br><br><div class="gmail_quote">On Sun, Jan 2, 2011 at 8:30 PM, Mark Abraham <span dir="ltr"><<a href="mailto:Mark.Abraham@anu.edu.au">Mark.Abraham@anu.edu.au</a>></span> wrote:<br>
<blockquote class="gmail_quote" style="margin: 0pt 0pt 0pt 0.8ex; border-left: 1px solid rgb(204, 204, 204); padding-left: 1ex;"><div class="im">On 3/01/2011 11:15 AM, Nancy wrote:<br>
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Hi All,<br>
<br>
I am performing molecular docking and molecular dynamics simulations of thiazolidinediones (TZDs) binding to the ligand binding domain of the PPAR-gamma receptor protein. The thiazolidinedione ring can exist in numerous different tautomeric states (see attached figure); is there any particular tautomer(s) that would be dominant, and thus most appropriate for docking and molecular dynamics simulations, at pH 7.4?<br>
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<br></div>
This sounds like the kind of question that is best answered by docking - and preferably only when the receptor site is not very flexible and lacks many titratable sites and lacks potential for water bridging. Any educated guesswork based on general chemical principles (or EM using MM or QM) will be doubtfully valid because of the specific steric and polarization contexts of the receptor site. I dunno if there are any sexy NMR techniques that can prune the list of candidates.<br>
<br>
Mark<div><div></div><div class="h5"><br>
<br>
<blockquote class="gmail_quote" style="margin: 0pt 0pt 0pt 0.8ex; border-left: 1px solid rgb(204, 204, 204); padding-left: 1ex;">
I have read the article "Metformin and glitazones: does similarity in biomolecular mechanism originate from tautomerism in these drugs?" J. Phys. Org. Chem. 2008, 21 30–33, as a reference, but it does make it clear as to which tautomer is most appropriate for simulating binding to a receptor protein at pH 7.4.<br>
<br>
Thanks in advance,<br>
Nancy<br>
<br>
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