Distributed automated docking of flexible ligands to proteins: parallel applications of AutoDock 2.4

J Comput Aided Mol Des. 1996 Aug;10(4):293-304. doi: 10.1007/BF00124499.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Azepines / chemistry
  • Azepines / metabolism
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism
  • Benzamidines / chemistry
  • Benzamidines / metabolism
  • Biotin / chemistry
  • Biotin / metabolism
  • Camphor / chemistry
  • Camphor / metabolism
  • Camphor 5-Monooxygenase / chemistry
  • Camphor 5-Monooxygenase / metabolism
  • Cluster Analysis
  • Computer Simulation
  • Crystallography, X-Ray
  • HIV Protease / chemistry
  • HIV Protease / metabolism
  • HIV Protease Inhibitors / chemistry
  • HIV Protease Inhibitors / metabolism
  • Hemagglutinins / chemistry
  • Hemagglutinins / metabolism
  • Immunoglobulin Fab Fragments / chemistry
  • Immunoglobulin Fab Fragments / metabolism
  • Ligands*
  • Molecular Conformation*
  • N-Acetylneuraminic Acid / chemistry
  • N-Acetylneuraminic Acid / metabolism
  • Phosphorylcholine / chemistry
  • Phosphorylcholine / metabolism
  • Protein Binding*
  • Protein Conformation
  • Software*
  • Streptavidin
  • Trypsin / chemistry
  • Trypsin / metabolism
  • User-Computer Interface

Substances

  • Azepines
  • Bacterial Proteins
  • Benzamidines
  • HIV Protease Inhibitors
  • Hemagglutinins
  • Immunoglobulin Fab Fragments
  • Ligands
  • XK 263
  • Phosphorylcholine
  • Biotin
  • Camphor
  • Streptavidin
  • Camphor 5-Monooxygenase
  • Trypsin
  • HIV Protease
  • N-Acetylneuraminic Acid
  • benzamidine