Document Detail

Binding mode prediction of cytochrome p450 and thymidine kinase protein-ligand complexes by consideration of water and rescoring in automated docking.
MedLine Citation:
PMID:  15801824     Owner:  NLM     Status:  MEDLINE    
The popular docking programs AutoDock, FlexX, and GOLD were used to predict binding modes of ligands in crystallographic complexes including X-ray water molecules or computationally predicted water molecules. Isoenzymes of two different enzyme systems were used, namely cytochromes P450 (n = 19) and thymidine kinases (n = 19) and three different "water" scenarios: i.e., docking (i) into water-free active sites, (ii) into active sites containing crystallographic water molecules, and (iii) into active sites containing water molecules predicted by a novel approach based on the program GRID. Docking accuracies were determined in terms of the root-mean-square deviation (RMSD) accuracy and, newly defined, in terms of the ligand catalytic site prediction (CSP) accuracy. Consideration of both X-ray and predicted water molecules and the subsequent pooling and rescoring of all solutions (generated by all three docking programs) with the SCORE scoring function significantly improved the quality of prediction of the binding modes both in terms of RMSD and CSP accuracy.
Chris de Graaf; Pavel Pospisil; Wouter Pos; Gerd Folkers; Nico P E Vermeulen
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  48     ISSN:  0022-2623     ISO Abbreviation:  J. Med. Chem.     Publication Date:  2005 Apr 
Date Detail:
Created Date:  2005-04-01     Completed Date:  2005-05-05     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2308-18     Citation Subset:  IM    
Leiden/Amsterdam Center for Drug Research, Division of Molecular Toxicology, Vrije Universiteit Amsterdam, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands.
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MeSH Terms
Catalytic Domain
Crystallography, X-Ray
Cytochrome P-450 Enzyme System / chemistry*
Isoenzymes / chemistry
Models, Molecular
Molecular Structure
Pharmaceutical Preparations / chemistry*
Protein Binding
Thymidine Kinase / chemistry*
Water / chemistry*
Reg. No./Substance:
0/Isoenzymes; 0/Ligands; 0/Pharmaceutical Preparations; 7732-18-5/Water; 9035-51-2/Cytochrome P-450 Enzyme System; EC Kinase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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