A Critical Assessment of Docking Programs and Scoring Functions

Docking is a computational technique that samples conformations of small molecules in protein binding
sites; scoring functions are used to assess which of these conformations best complements the protein binding
site. An evaluation of 10 docking programs and 37 scoring functions was conducted against eight proteins
of seven protein types for three tasks:  binding mode prediction, virtual screening for lead identification,
and rank-ordering by affinity for lead optimization. All of the docking programs were able to generate
ligand conformations similar to crystallographically determined protein/ligand complex structures for at
least one of the targets. However, scoring functions were less successful at distinguishing the crystallographic
conformation from the set of docked poses. Docking programs identified active compounds from a
pharmaceutically relevant pool of decoy compounds; however, no single program performed well for all of
the targets. For prediction of compound affinity, none of the docking programs or scoring functions made
a useful prediction of ligand binding affinity.