title: A critical assessment of docking programs and scoring functions.
abstract: 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.
authors.affiliation: GlaxoSmithKline Pharmaceuticals, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426, USA. Gregory.L.Warren@gsk.com
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Warren
authors.forename: C Webster
authors.initials: CW
authors.lastname: Andrews
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Capelli
authors.forename: Brian
authors.initials: B
authors.lastname: Clarke
authors.forename: Judith
authors.initials: J
authors.lastname: LaLonde
authors.forename: Millard H
authors.initials: MH
authors.lastname: Lambert
authors.forename: Mika
authors.initials: M
authors.lastname: Lindvall
authors.forename: Neysa
authors.initials: N
authors.lastname: Nevins
authors.forename: Simon F
authors.initials: SF
authors.lastname: Semus
authors.forename: Stefan
authors.initials: S
authors.lastname: Senger
authors.forename: Giovanna
authors.initials: G
authors.lastname: Tedesco
authors.forename: Ian D
authors.initials: ID
authors.lastname: Wall
authors.forename: James M
authors.initials: JM
authors.lastname: Woolven
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Peishoff
authors.forename: Martha S
authors.initials: MS
authors.lastname: Head
mesh_terms: D000465:Algorithms; D001665:Binding Sites; D015195:Drug Design; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship; D012984:Software
chemical_list: D008024:Ligands; D011506:Proteins