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 <[email protected]>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 >> >> > -- > gmx-users mailing list [email protected] > http://lists.gromacs.org/mailman/listinfo/gmx-users > Please search the archive at > http://www.gromacs.org/Support/Mailing_Lists/Search before posting! > Please don't post (un)subscribe requests to the list. Use the www interface > or send it to [email protected]. > Can't post? Read http://www.gromacs.org/Support/Mailing_Lists >
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