AMBER Archive (2002)

Subject: Re: mm_pbsa positive binding energies

From: David A. Case (case_at_scripps.edu)
Date: Mon Sep 02 2002 - 12:50:30 CDT

On Mon, Sep 02, 2002, Mathy Froeyen wrote:
>
> We did some mm_pbsa calculations.
>
> The resulting final free energy differences
> are positive ( using the Poisson Boltzman (PB) option).
>
> We expect negative dG values
> because the binding of the ligand to the receptor
> happens in the micromolar range.
>
> We obtain similar results for other ligands.
>
> We think that it has something to do with the fact that
> our ligands are (-) charged and there are also counterions present
> in the receptor.
>

I think this is not an uncommon observation. See, e.g.

%A C. Reyes
%A P. Kollman
%T Investigating the Binding Specificity of U1A-RNA by Computational
Mutagenesis
%J J. Mol. Biol.
%V 295
%P 1-6
%D 2000

%A C. Reyes
%A P. Kollman
%T Structure and Thermodynamics of RNA-protein Binding: Using Molecular
Dynamics and Free Energy Analyses to Calculate the Free Energies of
Binding and Conformational Change
%J J. Mol. Biol.
%V 297
%P 1145-1158
%D 2000

%A 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

..hope this helps...dac 

-- 

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