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On 3/01/2011 12:54 PM, Nancy wrote:
<blockquote
cite="mid:AANLkTim-Awqqjf4XaRM9HYoeO-Df=Xj1mnnYk5qEAqkT@mail.gmail.com"
type="cite">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?</blockquote>
<br>
I see the diol conformers would be aromatic, however do note that
thiophene is less aromatic than furan, so perhaps the aromaticity is
not a strong effect here.<br>
<br>
<blockquote
cite="mid:AANLkTim-Awqqjf4XaRM9HYoeO-Df=Xj1mnnYk5qEAqkT@mail.gmail.com"
type="cite"> Also, how could one start docking without a properly
defined ligand?<br>
</blockquote>
<br>
As you would for any ligand for which ligand conformation would not
be an issue - by supplying some kind of coordinate file. Here,
however, you will need to try several conformations systematically.
Note that this is fairly off-topic for this list, so please consult
the resources of your docking program for details.<br>
<br>
Mark<br>
<br>
<blockquote
cite="mid:AANLkTim-Awqqjf4XaRM9HYoeO-Df=Xj1mnnYk5qEAqkT@mail.gmail.com"
type="cite">
<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 moz-do-not-send="true"
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>
<blockquote class="gmail_quote" style="margin: 0pt 0pt 0pt
0.8ex; border-left: 1px solid rgb(204, 204, 204);
padding-left: 1ex;">
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>
</blockquote>
<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 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>
</blockquote>
<br>
</div>
</div>
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