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PMID: 7608743 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Flexible ligand docking using a genetic algorithm.

Journal of computer-aided molecular design ·Vol. 9 ·No. 2 ·1995-04-00 ·Pages 113-30

Oshiro CM, Kuntz ID, Dixon JS

Abstract

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.

MeSH Terms
Algorithms Crystallography, X-Ray Enzymes/chemistry,metabolism HIV Protease/chemistry,metabolism Haloperidol/analogs & derivatives,chemistry,metabolism Ligands Methotrexate/chemistry,metabolism Models, Genetic Models, Molecular Molecular Conformation Phenolphthalein Phenolphthaleins/chemistry,metabolism Protein Conformation Tetrahydrofolate Dehydrogenase/chemistry,metabolism Thymidylate Synthase/chemistry,metabolism
Chemicals
Enzymes Ligands Phenolphthaleins thioketal haloperidol Phenolphthalein Tetrahydrofolate Dehydrogenase Thymidylate Synthase HIV Protease Haloperidol Methotrexate
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Oshiro C M
Department of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco 94143-0446, USA.
Kuntz I D
Dixon J S
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Article Info
Journal
Journal of computer-aided molecular design
Abbr.
J Comput Aided Mol Des
ISSN
0920-654X
DOI
10.1007/BF00124402
Published
1995-04-00
Pages
113-30
Language
English
Region
Netherlands
NLM ID
8710425
Subset
IM
Grants
NIGMS NIH HHS · GM-31497 · United States
NIGMS NIH HHS · GM-39552 · United States
External Links
PubMed source DOI: 10.1007/BF00124402 View journal details
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