title: Development and validation of a modular, extensible docking program: DOCK 5.
abstract: We report on the development and validation of a new version of DOCK. The algorithm has been rewritten in a modular format, which allows for easy implementation of new scoring functions, sampling methods and analysis tools. We validated the sampling algorithm with a test set of 114 protein-ligand complexes. Using an optimized parameter set, we are able to reproduce the crystal ligand pose to within 2 A of the crystal structure for 79% of the test cases using our rigid ligand docking algorithm with an average run time of 1 min per complex and for 72% of the test cases using our flexible ligand docking algorithm with an average run time of 5 min per complex. Finally, we perform an analysis of the docking failures in the test set and determine that the sampling algorithm is generally sufficient for the binding pose prediction problem for up to 7 rotatable bonds; i.e. 99% of the rigid ligand docking cases and 95% of the flexible ligand docking cases are sampled successfully. We point out that success rates could be improved through more advanced modeling of the receptor prior to docking and through improvement of the force field parameters, particularly for structures containing metal-based cofactors.
authors.affiliation: Joint Graduate Program in Bioengineering, University of California, San Francisco, 600 16th Street, Genentech Hall, Box 2240, San Francisco, CA 94143, USA.
authors.forename: Demetri T
authors.initials: DT
authors.lastname: Moustakas
authors.forename: P Therese
authors.initials: PT
authors.lastname: Lang
authors.forename: Scott
authors.initials: S
authors.lastname: Pegg
authors.forename: Eric
authors.initials: E
authors.lastname: Pettersen
authors.forename: Irwin D
authors.initials: ID
authors.lastname: Kuntz
authors.forename: Natasja
authors.initials: N
authors.lastname: Brooijmans
authors.forename: Robert C
authors.initials: RC
authors.lastname: Rizzo
mesh_terms: D000465:Algorithms; D001665:Binding Sites; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D030562:Databases, Protein; D015195:Drug Design; D006860:Hydrogen Bonding; D008024:Ligands; D011485:Protein Binding; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D012984:Software
chemical_list: D008024:Ligands; D011506:Proteins