Re: AMBER: Explicit water in implicit enviornment?

From: Carlos Simmerling <>
Date: Mon, 17 Sep 2007 11:35:58 -0400

a google search for
water mm-pbsa
will turn up some discussions on this in the archive.

On 9/9/07, Hayden Eastwood <> wrote:
> Dear AMBER users
> I am calculating binding energies of 4 ligands with a target protein.
> However, I wish to compare these binding energies with that of the
> ligand-free form of the protein in which the binding pocket is known
> experimentally to house 4 water molecules.
> I have calculated the binding energy of each of the ligands using the
> generalized born model (igb=2) from the crystal structure via an ordinary
> minmization with sander. However, when considering the ligand-free form of
> the protein, I have used explicit water (TIP3).
> My questions is therefore:
> Is it meaningful to obtain the energy of the explicit water in the binding
> pocket when the system is immersed in a continuum solvent?
> The reason I am doing this and not just examining an empty binding pocket
> in
> an implicit environment is because I believe that hydrogen bonding plays a
> major role in stabilising the pocket, and the GB model (as I understand
> it)
> could never accurrately account for the specific hydrogen bonding
> framework.
> Am I right in assuming that the source of the inaccuracy (in examning
> explicit water in an implicit solvent) would arise largely from the GB
> model
> attempting to compute the non-polar contribution of the solvation free
> energy for each explicit water particle? I say this because my
> understanding
> is that the the non-polar contribution is derived via a surface-area
> weighted proportion of an empirically derived organic molecule (that does
> not share such properties with a single water particle.)
> Any ideas as to how best to model H-bonding in the pocket, whilst still
> maintaining the energetics associated with immersion in bulk water?
> Many thanks
> Hayden Eastwood
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Received on Wed Sep 19 2007 - 06:07:21 PDT
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