MM-GB/SA rescoring of docking poses.

ABSTRACT

The critical issues in docking include the prediction of the correct binding pose and the accurate estimation of the corresponding binding affinity. Different docking methodologies have all been successful in reproducing the crystallographic binding modes, but struggle when predicting the corresponding binding affinities. The rescoring of docking poses using the MM-GB/SA technique has emerged as an important computational approach in structure-based lead optimization as it provides for congeneric molecules, clearly superior correlations with experimental data to those obtained with typical docking scoring functions. Although the technique has been collectively referred as MM-GB/SA, there are in fact many flavors in the literature. Here we describe the details of our MM-GB/SA scoring protocol, highlighting not only its strengths but also the limitations.