Re: [AMBER] selecting the best docking pose with MM/PBSA

From: Ray Luo, Ph.D. <ray.luo.uci.edu>
Date: Tue, 9 Dec 2014 10:54:53 -0800

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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Received on Tue Dec 09 2014 - 11:00:02 PST