AMBER Archive (2005)

Subject: Re: AMBER: molecular dynamics simulation of protein containing Mg2+ cation

From: David A. Case (case_at_scripps.edu)
Date: Sun Jul 03 2005 - 18:34:14 CDT

On Fri, Jul 01, 2005, Ye Mei wrote:
>
> I am studying HIV-1 integrase, which contains a Mg2+ cation. Both D64 and
> D116 coordinate to this Mg2+ cation, together with water molecules and
> sometimes also with a ligand.
> This coordination will strongly effect the charge distribution among Mg2+,
> D64, D116 and other coordinated molecules. I used the default FF03
> parameters for all these residues, but it gave a very strong interaction
> between Mg2+ and a neutral ligand, like -150 Kcal/mol or even more. The
> ligand coordinate to Mg2+ with only 2 oxygen atoms, so -150 Kcal/mol, which
> mainly comes from coulomb interaction, is quite unreasonable. If we consider
> the charge redistribution among all these residues, the interaction should
> decrease.

There are a number of simulations in the literative on HIV integrase, and you
might look at what has been done there. One other example of Mg coordination
is in the following papers:

%A H. Gohlke
%A C. Kiel
%A D.A. Case
%T Insights into Protein-Protein Binding by Binding Free Energy Calculation
and Free Energy Decomposition for the Ras-Raf and Ras-RalGDS Complexes
%J J. Mol. Biol.
%V 330
%P 891-913
%D 2003

%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

But, as you point out, there is no simple way to handle divalent ions in
(current) molecular mechanics force fields that is fully satisfactory.

...dac
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