[Chimera-users] Thiazolidinedione Tautomers

[Elaine Meng]

Hi Nancy,
This isn't really a Chimera question -- you may have better luck if you try asking on the Comp Chem List (see ccl.net) or a docking forum such as dock-fans at mailman.docking.org

I don't know the answer.  The only other ideas I have are to consider any knowledge of which residues are important for binding, take a look at solved complexes with similar ligands (if any), and try to find more papers discussing the detailed interactions between such ligands and their receptors or other binding proteins.  The tautomer in the binding site may not be the same one that is dominant in solution.  You might just want to dock them all, if computer resources allow.

Good luck,
Elaine
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Elaine C. Meng, Ph.D. 
UCSF Computer Graphics Lab (Chimera team) and Babbitt Lab
Department of Pharmaceutical Chemistry
University of California, San Francisco

On Jan 2, 2011, at 4:15 PM, 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?
> 
> 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
>