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PMID: 12638011 Published · ppublish English Comparative Study Journal Article

Binding site characteristics in structure-based virtual screening: evaluation of current docking tools.

Journal of molecular modeling ·Vol. 9 ·No. 1 ·2003-02-00 ·Pages 47-57

Schulz-Gasch T, Stahl M

Abstract

Two new docking programs FRED (OpenEye Scientific Software) and Glide (Schrödinger, Inc.) in combination with various scoring functions implemented in these programs have been evaluated against a variety of seven protein targets (cyclooxygenase-2, estrogen receptor, p38 MAP kinase, gyrase B, thrombin, gelatinase A, neuraminidase) in order to assess their accuracy in virtual screening. Sets of known inhibitors were added to and ranked relative to a random library of drug-like compounds. Performance was compared in terms of enrichment factors and CPU time consumption. Results and specific features of the two new tools are discussed and compared to previously published results using FlexX (Tripos, Inc.) as a docking engine. In addition, general criteria for the selection of docking algorithms and scoring functions based on binding-site characteristics of specific protein targets are proposed. Figure Enrichment factors obtained with FlexX, Glide and FRED docking engines in combination with different scoring functions for seven selected targets with highly variable binding sites

MeSH Terms
Algorithms Binding Sites Cyclooxygenase 2/chemistry,metabolism DNA Gyrase/chemistry,metabolism Enzyme Inhibitors/chemistry,metabolism Matrix Metalloproteinase 2/chemistry,metabolism Models, Molecular Molecular Structure Neuraminidase/chemistry,metabolism Protein Binding Proteins/chemistry,metabolism Receptors, Estrogen/chemistry,metabolism Software Software Validation Thrombin/chemistry,metabolism p38 Mitogen-Activated Protein Kinases/chemistry,metabolism
Chemicals
Enzyme Inhibitors Proteins Receptors, Estrogen Cyclooxygenase 2 p38 Mitogen-Activated Protein Kinases Neuraminidase Thrombin Matrix Metalloproteinase 2 DNA Gyrase
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Schulz-Gasch Tanja
Pharmaceuticals Division, Molecular Design, F. Hoffmann-La Roche Ltd, 4070, Basel, Switzerland. Tanja.Schulz-Gasch@roche.com
Stahl Martin
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Article Info
Journal
Journal of molecular modeling
Abbr.
J Mol Model
ISSN
0948-5023
DOI
10.1007/s00894-002-0112-y
Email
tanja.schulz-gasch@roche.com
Published
2003-02-00
Epub
2003-00-14
Pages
47-57
Language
English
Region
Germany
NLM ID
9806569
Subset
IM
External Links
PubMed source DOI: 10.1007/s00894-002-0112-y View journal details
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