GEMDOCK: A Generic Evolutionary Method for Molecular Docking

Jinn-Moon Yang*, Chun Chen Chen

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

382 Scopus citations

Abstract

We have developed an evolutionary approach for flexible ligand docking. This approval, GEMDOCK, uses a Generic Evolutionary Method for molecular DOCKing and an empirical scoring function. The former combines both discrete and continuous global search strategies with local search strategies to speed up convergence, whereas the latter results in rapid recognition of potential ligands. GEMDOCK was tested on a diverse data set of 100 protein-ligand complexes from the Protein Data Bank. In 79% of these complexes, the docked lowest energy ligand structures had root-mean-square derivations (RMSDs) below 2.0 Å with respect to the corresponding crystal structures. The success rate increased to 85% if the structure water molecules were retained. We evaluated GEMDOCK on two cross-docking experiments in which each ligand of a protein ensemble was docked into each protein of the ensemble. Seventy-six percent of the docked structures had RMSDs below 2.0 A when the ligands were docked into foreign structures. We analyzed and validated GEMDOCK with respect to various search spaces and scoring functions, and found that if the scoring function was perfect, then the predicted accuracy was also essentially perfect. This study suggests that GEMDOCK is a useful tool for molecular recognition and may be used to systematically evaluate and thus improve scoring functions.

Original languageEnglish
Pages (from-to)288-304
Number of pages17
JournalProteins: Structure, Function and Genetics
Volume55
Issue number2
DOIs
StatePublished - 1 May 2004

Keywords

  • Cross-docking
  • Evolutionary algorithm
  • Hybrid docking
  • Molecular recognition
  • Protein-ligand docking
  • Structure-based drug design

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