Distributed automated docking of flexible ligands to proteins: parallel applications of AutoDock 2.4.
AutoDock 2.4 predicts the bound conformations of a small, flexible ligand to a nonflexible macromolecular target of known structure. The technique combines simulated annealing for conformation searching with a rapid grid-based method of energy evaluation based on the AMBER force field. AutoDock has been optimized in performance without sacrificing accuracy; it incorporates many enhancements and additions, including an intuitive interface. We have developed a set of tools for launching and analyzing many independent docking jobs in parallel on a heterogeneous network of UNIX-based workstations. This paper describes the current release, and the results of a suite of diverse test systems. We also present the results of a systematic investigation into the effects of varying simulated-annealing parameters on molecular docking. We show that even for ligands with a large number of degrees of freedom, root-mean-square deviations of less than 1 A from the crystallographic conformation are obtained for the lowest-energy dockings, although fewer dockings find the crystallographic conformation when there are more degrees of freedom.
Morris
G M
GM
Department of Molecular Biology, MB-5, Scripps Research Institute, La Jolla, CA 92037, USA.
Goodsell
D S
DS
Huey
R
R
Olson
A J
AJ
D001381:Azepines / Q000737:chemistry / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D001550:Benzamidines / Q000737:chemistry / Q000378:metabolism; D001710:Biotin / Q000737:chemistry / Q000378:metabolism; D002164:Camphor / Q000737:chemistry / Q000378:metabolism; D019475:Camphor 5-Monooxygenase / Q000737:chemistry / Q000378:metabolism; D016000:Cluster Analysis; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D016333:HIV Protease / Q000737:chemistry / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000737:chemistry / Q000378:metabolism; D006388:Hemagglutinins / Q000737:chemistry / Q000378:metabolism; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D008968:Molecular Conformation; D019158:N-Acetylneuraminic Acid / Q000737:chemistry / Q000378:metabolism; D010767:Phosphorylcholine / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D012984:Software; D019809:Streptavidin; D014357:Trypsin / Q000737:chemistry / Q000378:metabolism; D014584:User-Computer Interface
D001381:Azepines; D001426:Bacterial Proteins; D001550:Benzamidines; D017320:HIV Protease Inhibitors; D006388:Hemagglutinins; D007140:Immunoglobulin Fab Fragments; D008024:Ligands; C104713:XK 263; D010767:Phosphorylcholine; D001710:Biotin; D002164:Camphor; D019809:Streptavidin; D019475:Camphor 5-Monooxygenase; D014357:Trypsin; D016333:HIV Protease; D019158:N-Acetylneuraminic Acid; C032157:benzamidine