title: Comparison of topological, shape, and docking methods in virtual screening.
abstract: Virtual screening benchmarking studies were carried out on 11 targets to evaluate the performance of three commonly used approaches: 2D ligand similarity (Daylight, TOPOSIM), 3D ligand similarity (SQW, ROCS), and protein structure-based docking (FLOG, FRED, Glide). Active and decoy compound sets were assembled from both the MDDR and the Merck compound databases. Averaged over multiple targets, ligand-based methods outperformed docking algorithms. This was true for 3D ligand-based methods only when chemical typing was included. Using mean enrichment factor as a performance metric, Glide appears to be the best docking method among the three with FRED a close second. Results for all virtual screening methods are database dependent and can vary greatly for particular targets.
authors.affiliation: Department of Molecular Systems, WP53F-301, Merck Research Laboratories, West Point, Pennsylvania 19486, USA. georgia_mcgaughey@merck.com
authors.forename: Georgia B
authors.initials: GB
authors.lastname: McGaughey
authors.forename: Robert P
authors.initials: RP
authors.lastname: Sheridan
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Bayly
authors.forename: J Chris
authors.initials: JC
authors.lastname: Culberson
authors.forename: Constantine
authors.initials: C
authors.lastname: Kreatsoulas
authors.forename: Stacey
authors.initials: S
authors.lastname: Lindsley
authors.forename: Vladimir
authors.initials: V
authors.lastname: Maiorov
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Truchon
authors.forename: Wendy D
authors.initials: WD
authors.lastname: Cornell
mesh_terms: D001665:Binding Sites; D002626:Chemistry, Pharmaceutical; D008024:Ligands; D015394:Molecular Structure
chemical_list: D008024:Ligands