Journal of Computer-Aided Molecular Design

, Volume 15, Issue 5, pp 411–428

DOCK 4.0: Search strategies for automated molecular docking of flexible molecule databases

  • Todd J.A. Ewing
  • Shingo Makino
  • A. Geoffrey Skillman
  • Irwin D. Kuntz
Article

DOI: 10.1023/A:1011115820450

Cite this article as:
Ewing, T.J., Makino, S., Skillman, A.G. et al. J Comput Aided Mol Des (2001) 15: 411. doi:10.1023/A:1011115820450

Abstract

In this paper we describe the search strategies developed for docking flexible molecules to macomolecular sites that are incorporated into the widely distributed DOCK software, version 4.0. The search strategies include incremental construction and random conformation search and utilize the existing Coulombic and Lennard-Jones grid-based scoring function. The incremental construction strategy is tested with a panel of 15 crystallographic testcases, created from 12 unique complexes whose ligands vary in size and flexibility. For all testcases, at least one docked position is generated within 2 Å of the crystallographic position. For 7 of 15 testcases, the top scoring position is also within 2 Å of the crystallographic position. The algorithm is fast enough to successfully dock a few testcases within seconds and most within 100 s. The incremental construction and the random search strategy are evaluated as database docking techniques with a database of 51 molecules docked to two of the crystallographic testcases. Incremental construction outperforms random search and is fast enough to reliably rank the database of compounds within 15 s per molecule on an SGI R10000 cpu.

database searchingflexible dockingincremental constructionmolecular dockingvirtual screening

Copyright information

© Kluwer Academic Publishers 2001

Authors and Affiliations

  • Todd J.A. Ewing
    • 1
  • Shingo Makino
    • 1
  • A. Geoffrey Skillman
    • 1
  • Irwin D. Kuntz
    • 1
  1. 1.Department of Pharmaceutical Chemistry, School of PharmacyUniversity of CaliforniaSan FranciscoUSA