(unknown charset) Re: AMBER: Mg2+ issues of using MM-PB/GBSA

From: (unknown charset) Thomas Cheatham <cheatham.chpc.utah.edu>
Date: Thu, 1 Dec 2005 22:27:21 -0700 (Mountain Standard Time)

> I wonder whether I can use MM-PB/GBSA method to calculate the binding
> free energy in the case of Mg2+ directly involving in the ligand
> binding. The initial tests showed that the energy difference calculated
> by different GB methods is up to ~80 kcal/mol, and the difference
> between GB and PB models is also quite large, over 50 kcal/mol. In
> addition, different Born radii of Mg2+ (from 0.99 ĘC 1.45) also seem
> giving various energies, ranging from -10 to -130 kcal/mol.

In the paper by Stefl et al. (Sponer/Cheatham) Biophys J. 83, 1787-1804 (2003)
we adopted the idea of fitting the radii to give the correct free energy
of solvation for Na+, or in other words, we adjusted the radii to give
~100 kcal/mol when used for an isolated Na+ ion and then used this when
doing the energy comparisons with MM-PBSA. If you read this paper,
including the detailed supplementary material, you can see how we did the
energy comparisons (only comparing energies calculated with equivalent
numbers of ions). In principle, this could be done with Mg2+, but as
Simmerling and Case pointed out, this is a research question and there may
be further complications with Mg2+ related to lack of explicit
polarization, etc.

\-/ Thomas E. Cheatham, III (Assistant Professor) College of Pharmacy
-/- Departments of Med. Chem. and of Pharmaceutics and Pharm. Chem.
/-\ Adjunct Asst Prof of Bioeng.; Center for High Performance Computing
\-/ University of Utah, 30 S 2000 E, SH 201, Salt Lake City, UT 84112
/-\ tec3.utah.edu (801) 587-9652; FAX: (801) 585-9119
\-/ BPRP295A http://www.chpc.utah.edu/~cheatham

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Received on Fri Dec 02 2005 - 05:53:01 PST
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