[Dock-fans] Thiazolidinedione Tautomers

Nancy nancy5villa at gmail.com
Tue Jan 4 16:38:23 PST 2011

Thanks for the info.  I would greatly appreciate it if anyone can provide as
much detail as possible as to which of the tautomer(s) is most stable in an
aqueous solution at ph 7.4.

Thanks in advance,

On Tue, Jan 4, 2011 at 5:12 PM, John Irwin <jir322 at gmail.com> wrote:

> Hi Nancy
> Of the two predictive methods we most commonly use, one consistently
> predicts the di-ketone form, the other predicts the tautomer having the
> hydroxyl between N and S. Fwiw, ZINC currently represents the  di-ketone
> form only in most cases I looked at.  Also fwiw, there are half a dozen
> cases of the di-ketone form in the CSD, and zero cases of the hydroxyl
> tautomer. That is weak evidence, because the ligand is not solvated in the
> small molecule crystal form. Still.
> In the crystal structure 2X5O, the ligand appears to be in the 2,4-dione
> form.
> Perhaps someone else on the list has an opinion (or even better, more
> data!). My suspicion is that both tautomers may be relevant, given the right
> complementary binding site.
> John
> On Tue, Jan 4, 2011 at 1:41 PM, Nancy <nancy5villa at gmail.com> wrote:
>> Hi All,
>> 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; is there any particular tautomer(s)
>> that would be dominant, and thus most appropriate for docking and molecular
>> dynamics simulations, at pH 7.4?
>> 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.
>> Thanks in advance,
>> Nancy
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