[gmx-users] Thiazolidinedione Tautomers

Mark Abraham Mark.Abraham at anu.edu.au
Mon Jan 3 08:42:00 CET 2011

On 3/01/2011 12:54 PM, Nancy wrote:
> Hi All,
> In the figure illustrating the various tautomers, some are actually 
> aromatic; wouldn't these be the predominant species at pH 7.4?

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.

>   Also, how could one start docking without a properly defined ligand?

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.


> Thanks in advance,
> Nancy
> On Sun, Jan 2, 2011 at 8:30 PM, Mark Abraham <Mark.Abraham at anu.edu.au 
> <mailto: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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