Benchmarking a novel ensemble docking method.

Abstract

Docking is an important tool in the kit of researchers and engineers working on molecular design and drug development problems. It is computationally efficient enough that it can be used on thousands or tens of thousands of structures with reasonable access to a cluster environment, and has the capacity to find binding poses and even estimate affinities. It has many well-known weaknesses, however. One significant weakness is that it does not properly account for conformational heterogeneity in receptors. This general weakness can produce incredibly poor results in cases where this heterogeneity changes the conformation of the binding site, since the receptor's ensemble can be mostly populated with states where the pocket of interest is closed (sterically occluded), as is the case with cryptic pockets.