AMBER Archive (2004)

Subject: Re: AMBER: MM-PBSA: molecular charges and active site water

From: David A. Case (
Date: Thu Feb 12 2004 - 22:06:56 CST

On Thu, Feb 12, 2004, Anselm Horn wrote:
> 1,
> Is the total charge of the system of crucial importance for MM-PBSA
> calculations, i.e. should both ligand and receptor be electrically neutral?
> Is there a problem, if the ligand and receptor have the same charge but
> opposite sign? However, counterions, when added to the complex, are to be
> excluded from the ligand/receptor definition in in any case.

There is no requirement in principle that the ligand or receptor be neutral.
But which charged interactions, is can be difficult to get a good balance
between solvent screening and the direct interactions, if for no other reason
that the "raw" interactions are so much larger than for uncharged systems.

> 2,
> My system contains some active site water molecules that are hidden from
> the rest of the solvent by the ligand/receptor environment. How do I
> include those in the MM-PBSA calculation? Is it feasable to make them
> belong to the receptor or do I have to treat the other case as well, where
> they belong to the ligand?

I don't know of any real research that answers this question; handling of
"bound" waters can be a real headache for mm-pbsa calculations.

A couple of (my) papers that deal with these problems are the following:

 V. Tsui
%A D.A. Case
%T Calculations of the Absolute Free Energies of Binding between RNA and Metal
%Ions Using Molecular Dynamics Simulations and Continuum Electrostatics
%J J. Phys. Chem. B
%V 105
%P 11314-11325
%D 2001

%A H. Gohlke
%A D.A. Case
%T Converging Free Energy Estimates: MM-PB(GB)SA Studies on the
%Protein-Protein Complex Ras-Raf
%J J. Comput. Chem.
%V 25
%P 238-250
%D 2004

...good luck...dac


================================================================== David A. Case | e-mail: Dept. of Molecular Biology, TPC15 | fax: +1-858-784-8896 The Scripps Research Institute | phone: +1-858-784-9768 10550 N. Torrey Pines Rd. | home page: La Jolla CA 92037 USA | ================================================================== ----------------------------------------------------------------------- The AMBER Mail Reflector To post, send mail to To unsubscribe, send "unsubscribe amber" to