Method for Computing Protein Binding Affinity

Charles Karney*

Sarnoff Corporation

A major challenge in computational drug discovery is to compute the binding affinity of a candidate drug molecule to a protein target. The difficulty comes from the necessity to include the change in the entropy as the drug molecule binds to the protein. Here we describe a practical Monte Carlo method to compute the binding affinity. Provided that an accurate protein structure is given, that the protein binding site is known, and that an accurate chemical force field together with a continuum solvation model is used, this method provides a quantitative estimate of the free energy of binding.

(*) In collaboration with:

Jason E. Ferrara (Sarnoff Corporation) and Stephan Brunner (Locus Pharmaceuticals)