Journal of Computer-Aided Molecular Design

, Volume 9, Issue 2, pp 113–130

Flexible ligand docking using a genetic algorithm

  • C. M. Oshiro
  • I. D. Kuntz
  • J. Scott Dixon
Research Papers

DOI: 10.1007/BF00124402

Cite this article as:
Oshiro, C.M., Kuntz, I.D. & Dixon, J.S. J Computer-Aided Mol Des (1995) 9: 113. doi:10.1007/BF00124402

Summary

Two computational techniques have been developed to explore the orientational and conformational space of a flexible ligand within an enzyme. Both methods use the Genetic Algorithm (GA) to generate conformationally flexible ligands in conjunction with algorithms from the DOCK suite of programs to characterize the receptor site. The methods are applied to three enzyme-ligand complexes: dihydrofolate reductase-methotrexate, thymidylate synthase-phenolpthalein and HIV protease-thioketal haloperidol. Conformations and orientations close to the crystallographically determined structures are obtained, as well as alternative structures with low energy. The potential for the GA method to screen a database of compounds is also examined. A collection of ligands is evaluated simultaneously, rather than docking the ligands individually into the enzyme.

Keywords

Genetic algorithm DOCK Flexible conformational search Protein-ligand interactions Dihydrofolate reductase Thymidylate synthase HIV protease 

Abbreviations

GA

genetic algorithm; dhfr, dihydrofolate reductase

mtx

methotrexate

ts

thymidylate synthase

fen

phenolphalein

HIV

human immune deficiency virus

hivp

HIV protease

thk

thioketal haloperidol

Copyright information

© ESCOM Science Publishers B.V 1995

Authors and Affiliations

  • C. M. Oshiro
    • 1
  • I. D. Kuntz
    • 1
  • J. Scott Dixon
    • 2
  1. 1.Department of Pharmaceutical Chemistry, School of PharmacyUniversity of CaliforniaSan FranciscoU.S.A.
  2. 2.Department of Physical and Structural ChemsitrySmithKline Beecham PharmaceuticalsKing of PrussiaU.S.A.

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