[gmx-users] Thiazolidinedione Tautomers

[Nancy]

Hi All,

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?

Thanks in advance,
Nancy


On Sun, Jan 2, 2011 at 8:30 PM, Mark Abraham <Mark.Abraham at anu.edu.au>wrote:

> On 3/01/2011 11:15 AM, Nancy 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 (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?
>>
>
> 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.
>
> Mark
>
>
>  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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