title: A comparison of heuristic search algorithms for molecular docking.
abstract: This paper describes the implementation and comparison of four heuristic search algorithms (genetic algorithm, evolutionary programming, simulated annealing and tabu search) and a random search procedure for flexible molecular docking. To our knowledge, this is the first application of the tabu search algorithm in this area. The algorithms are compared using a recently described fast molecular recognition potential function and a diverse set of five protein-ligand systems. Statistical analysis of the results indicates that overall the genetic algorithm performs best in terms of the median energy of the solutions located. However, tabu search shows a better performance in terms of locating solutions close to the crystallographic ligand conformation. These results suggest that a hybrid search algorithm may give superior results to any of the algorithms alone.
authors.affiliation: Proteus Molecular Design Ltd., Macclesfield, Cheshire, U.K.
authors.forename: D R
authors.initials: DR
authors.lastname: Westhead
authors.forename: D E
authors.initials: DE
authors.lastname: Clark
authors.forename: C W
authors.initials: CW
authors.lastname: Murray
mesh_terms: D000465:Algorithms; D001120:Arginine / Q000031:analogs & derivatives; D001381:Azepines / Q000737:chemistry; D001665:Binding Sites; D003198:Computer Simulation; D004151:Dipeptides / Q000737:chemistry; D016333:HIV Protease / Q000737:chemistry; D008024:Ligands; D046911:Macromolecular Substances; D008727:Methotrexate / Q000737:chemistry; D008958:Models, Molecular; D009439:Neuraminidase / Q000737:chemistry; D010875:Pipecolic Acids / Q000737:chemistry; D010880:Piperidines / Q000737:chemistry; D011485:Protein Binding; D012985:Software Design; D013329:Structure-Activity Relationship; D013449:Sulfonamides; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry; D013816:Thermodynamics; D013917:Thrombin / Q000737:chemistry
chemical_list: D001381:Azepines; D004151:Dipeptides; D008024:Ligands; D046911:Macromolecular Substances; D010875:Pipecolic Acids; D010880:Piperidines; D013449:Sulfonamides; C104713:XK 263; C038708:N(alpha)-(2-naphthylsulfonylglycyl)-4-amidinophenylalanine piperidide; D001120:Arginine; D013762:Tetrahydrofolate Dehydrogenase; D009439:Neuraminidase; D013917:Thrombin; D016333:HIV Protease; C031942:argatroban; D008727:Methotrexate