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Flexible ligand docking using a robust evolutionary algorithm
Author(s) -
Yang JinnMoon,
Kao ChengYan
Publication year - 2000
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/1096-987x(200008)21:11<988::aid-jcc8>3.0.co;2-h
Subject(s) - docking (animal) , evolutionary algorithm , dihydrofolate reductase , ligand (biochemistry) , chemistry , computer science , computational chemistry , algorithm , stereochemistry , mathematics , mathematical optimization , enzyme , biochemistry , receptor , nursing , medicine
A flexible ligand docking protocol based on evolutionary algorithms is investigated. The proposed approach incorporates family competition and adaptive rules to integrate decreasing‐based mutations and self‐adaptive mutations to act as global and local search strategies, respectively. The method is applied to a dihydrofolate reductase enzyme with the anticancer drug methotrexate and two analogues of antibacterial drug trimethoprim. Conformations and orientations closed to the crystallographically determined structures are obtained, as well as alternative structures with low energy. Numerical results indicate that the new approach is very robust. The docked lowest‐energy structures have root‐mean‐square derivations ranging from 0.67 to 1.96 Å with respect to the corresponding crystal structures. © 2000 John Wiley & Sons, Inc. J Comput Chem 21: 988–998, 2000