title: Comparative performance of several flexible docking programs and scoring functions: enrichment studies for a diverse set of pharmaceutically relevant targets.
abstract: Virtual screening by molecular docking has become a widely used approach to lead discovery in the pharmaceutical industry when a high-resolution structure of the biological target of interest is available. The performance of three widely used docking programs (Glide, GOLD, and DOCK) for virtual database screening is studied when they are applied to the same protein target and ligand set. Comparisons of the docking programs and scoring functions using a large and diverse data set of pharmaceutically interesting targets and active compounds are carried out. We focus on the problem of docking and scoring flexible compounds which are sterically capable of docking into a rigid conformation of the receptor. The Glide XP methodology is shown to consistently yield enrichments superior to the two alternative methods, while GOLD outperforms DOCK on average. The study also shows that docking into multiple receptor structures can decrease the docking error in screening a diverse set of active compounds.
authors.affiliation: BioMaPS Institute for Quantitative Biology, Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, USA.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Zhou
authors.forename: Anthony K
authors.initials: AK
authors.lastname: Felts
authors.forename: Richard A
authors.initials: RA
authors.lastname: Friesner
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Levy
mesh_terms: D003461:Crystallography; D008024:Ligands; D008958:Models, Molecular; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry
chemical_list: D008024:Ligands; D004364:Pharmaceutical Preparations; D011506:Proteins