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*
> > _______________________________________________
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>
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>
--
======================================================================
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*
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Received on Tue Dec 09 2014 - 14:00:02 PST
