Comparison of topological, shape, and docking methods in virtual screening.
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.
McGaughey
Georgia B
GB
Department of Molecular Systems, WP53F-301, Merck Research Laboratories, West Point, Pennsylvania 19486, USA. georgia_mcgaughey@merck.com
Sheridan
Robert P
RP
Bayly
Christopher I
CI
Culberson
J Chris
JC
Kreatsoulas
Constantine
C
Lindsley
Stacey
S
Maiorov
Vladimir
V
Truchon
Jean-Francois
JF
Cornell
Wendy D
WD
D001665:Binding Sites; D002626:Chemistry, Pharmaceutical; D008024:Ligands; D015394:Molecular Structure
D008024:Ligands