Subject: Re: CCL:Predicting protein-ligand structures.

From: "Peter Shenkin" <[email-masked]>
Date: Tue, 28 Mar 1995 18:58:32 -0500

On Mar 27,  3:39pm, Michael K. Gilson wrote:
> Subject: CCL:Predicting protein-ligand structures.

> Given a flexible ligand and a relatively rigid protein whose 3-D
> structure in the absence of the ligand is known, is there a way of
> reliably generating a several-thousand member (or smaller) set of
> protein-ligand complex structures, which is highly likely to include
> something close (say 1.5 Angstrom RMSD) to the true structure of the
> complex?

Hi, Mike,

Any molecular mechanics program which can do a conformational search
in a multimolecular context (i.e., varying the relative positions/
orientation of the molecules as well as internal degrees of freedom)
can generate such an ensemble.

The question that arises is:  "Which of the several thousands of docking
configurations produces are 'important'?"  If one is to try to reliably
pick the best configurations out of the ensemble, much may hinge on
how well solvent effects are handled, and on how well the relative free-
energies can be obtained, or can be reliably correlated with the molecular-
mechanics energies.

In any case, MacroModel/BatchMin can do this type of calculation, using
an implicit solvation model based in part on your own work!  I'm sure
other programs address this problem as well.

	-P.

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