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 lig and to a nonflexible macromolecular target of known structure. The tec hnique 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 a n intuitive interface. We have developed a set of tools for launching and analyzing many independent docking jobs in parallel on a heterogen eous network of UNIX-based workstations. This paper describes the curr ent release, and the results of a suite of diverse test systems. We al so present the results of a systematic investigation into the effects of varying simulated-annealing parameters on molecular docking. We sho w that even for ligands with a large number of degrees of freedom, roo t-mean-square deviations of less than 1 Angstrom from the crystallogra phic conformation are obtained for the lowest-energy dockings, althoug h fewer dockings find the crystallographic conformation when there are more degrees of freedom.