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-- Ray Luo, Ph.D. Professor, Biochemistry, Molecular Biophysics, Chemical Physics, Chemical and Biomedical Engineering University of California, Irvine, CA 92697-3900 On Tue, Dec 9, 2014 at 1:32 PM, Thomas Evangelidis <tevang3.gmail.com> wrote: > Hi Prof. Luo, > > What about net charge? 2 of the tautomers of the ligand have +1 and +2 > charge, respectively. Does this have a negative impact on binding free > energy predictions? This paper for instance states that charges at the > binding interface impair the GB model predictions: > > http://pubs.acs.org/doi/abs/10.1021/jp5015934 > > thanks, > Thomas > > > On 9 December 2014 at 20:54, Ray Luo, Ph.D. <ray.luo.uci.edu> wrote: > >> Hi Thomas, >> >> JM2C. >> >> I theory, the method should work. The practical issue is that these >> three binding poses maybe interchangeable during MD simulations, so it >> becomes hard to know for which pose you are computing delta G … >> >> However, I would like to point out that there are successes reported >> for using the energy model (i.e. AMBER/PBSA) in ranking compounds >> binding to the same receptor when only minimization was used (without >> averaging over MD snapshots). It can also rank single-point mutant >> stabilities in a similar manner (i.e. without MD) >> >> So I think it's a very good scientific exercise to see whether you can >> use the energy model to rank your binding poses after minimization. >> It's also a reasonable direction to explore a short MD that does not >> cause dramatic binding poses change in this effort. >> >> Ray >> -- >> Ray Luo, Ph.D. >> Professor, >> Biochemistry, Molecular Biophysics, Chemical Physics, >> Chemical and Biomedical Engineering >> University of California, Irvine, CA 92697-3900 >> >> >> On Mon, Dec 8, 2014 at 3:22 PM, Thomas Evangelidis <tevang3.gmail.com> >> wrote: >> > Dear AMBER list, >> > >> > I have 3 posing docking poses of a compound. Does calculating relative >> free >> > energies of binding with MM/PBSA (without the normal mode approximation) >> > help selecting the predominant one? I know MM/PBSA makes a lot of very >> > large assumptions and the differences in the final relative free energies >> > may be within the error of the method. There is also a dependence on the >> > ligand force field which determines how strained a conformation is in the >> > protein. I am just curious to know if other people use this methods to >> > select the best among a few docking poses. >> > >> > thanks in advance, >> > Thomas >> > >> > >> > >> > -- >> > >> > ====================================================================== >> > >> > Thomas Evangelidis >> > >> > PhD student >> > University of Athens >> > Faculty of Pharmacy >> > Department of Pharmaceutical Chemistry >> > Panepistimioupoli-Zografou >> > 157 71 Athens >> > GREECE >> > >> > email: tevang.pharm.uoa.gr >> > >> > tevang3.gmail.com >> > >> > >> > website: https://sites.google.com/site/thomasevangelidishomepage/ >> > >> > =============================================================== >> > >> > *Physics is the only real science. The rest are just stamp collecting.* >> > >> > *- Ernest Rutherford* >> > _______________________________________________ >> > AMBER mailing list >> > AMBER.ambermd.org >> > http://lists.ambermd.org/mailman/listinfo/amber >> >> _______________________________________________ >> AMBER mailing list >> AMBER.ambermd.org >> http://lists.ambermd.org/mailman/listinfo/amber >> > > > > -- > > ====================================================================== > > Thomas Evangelidis > > PhD student > University of Athens > Faculty of Pharmacy > Department of Pharmaceutical Chemistry > Panepistimioupoli-Zografou > 157 71 Athens > GREECE > > email: tevang.pharm.uoa.gr > > tevang3.gmail.com > > > website: https://sites.google.com/site/thomasevangelidishomepage/ > > =============================================================== > > *Physics is the only real science. The rest are just stamp collecting.* > > *- Ernest Rutherford* > _______________________________________________ > AMBER mailing list > AMBER.ambermd.org > http://lists.ambermd.org/mailman/listinfo/amber _______________________________________________ AMBER mailing list AMBER.ambermd.org http://lists.ambermd.org/mailman/listinfo/amberReceived on Tue Dec 09 2014 - 16:00:03 PST