title: Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy.
abstract: Unlike other methods for docking ligands to the rigid 3D structure of a known protein receptor, Glide approximates a complete systematic search of the conformational, orientational, and positional space of the docked ligand. In this search, an initial rough positioning and scoring phase that dramatically narrows the search space is followed by torsionally flexible energy optimization on an OPLS-AA nonbonded potential grid for a few hundred surviving candidate poses. The very best candidates are further refined via a Monte Carlo sampling of pose conformation; in some cases, this is crucial to obtaining an accurate docked pose. Selection of the best docked pose uses a model energy function that combines empirical and force-field-based terms. Docking accuracy is assessed by redocking ligands from 282 cocrystallized PDB complexes starting from conformationally optimized ligand geometries that bear no memory of the correctly docked pose. Errors in geometry for the top-ranked pose are less than 1 A in nearly half of the cases and are greater than 2 A in only about one-third of them. Comparisons to published data on rms deviations show that Glide is nearly twice as accurate as GOLD and more than twice as accurate as FlexX for ligands having up to 20 rotatable bonds. Glide is also found to be more accurate than the recently described Surflex method.
authors.affiliation: Department of Chemistry, Columbia University, New York, New York 10036, USA. rich@chem.columbia.edu
authors.forename: Richard A
authors.initials: RA
authors.lastname: Friesner
authors.forename: Jay L
authors.initials: JL
authors.lastname: Banks
authors.forename: Robert B
authors.initials: RB
authors.lastname: Murphy
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Halgren
authors.forename: Jasna J
authors.initials: JJ
authors.lastname: Klicic
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Mainz
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Repasky
authors.forename: Eric H
authors.initials: EH
authors.lastname: Knoll
authors.forename: Mee
authors.initials: M
authors.lastname: Shelley
authors.forename: Jason K
authors.initials: JK
authors.lastname: Perry
authors.forename: David E
authors.initials: DE
authors.lastname: Shaw
authors.forename: Perry
authors.initials: P
authors.lastname: Francis
authors.forename: Peter S
authors.initials: PS
authors.lastname: Shenkin
mesh_terms: D001665:Binding Sites; D015195:Drug Design; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D009010:Monte Carlo Method; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship; D013816:Thermodynamics; D013937:Thymidine Kinase / Q000737:chemistry
chemical_list: D008024:Ligands; D011506:Proteins; D013937:Thymidine Kinase