Cited by 10,057Computational Drug Discovery MethodsProtein Structure and DynamicsAdvanced Chemical Physics Studies

Glide: A new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy

Friesner, Richard A., Banks, Jay L., Murphy, Robert B., Halgren, Thomas A., Klicic, Jasna J., Mainz, Daniel T., Repasky, Matthew P., Knoll, Eric H. +5 more·2004·Journal of Medicinal Chemistry

Abstract

Unlike other methods for docking ligands to the rigid 3D structure of a known protein receptor, Glide approximates a complete systematic search of the conformational, orientational, and positional space of the docked ligand. In this search, an initial rough positioning and scoring phase that dramatically narrows the search space is followed by torsionally flexible energy optimization on an OPLS-AA nonbonded potential grid for a few hundred surviving candidate poses. The very best candidates are further refined via a Monte Carlo sampling of pose conformation; in some cases, this is crucial to obtaining an accurate docked pose. Selection of the best docked pose uses a model energy function that combines empirical and force-field-based terms. Docking accuracy is assessed by redocking ligands from 282 cocrystallized PDB complexes starting from conformationally optimized ligand geometries that bear no memory of the correctly docked pose. Errors in geometry for the top-ranked pose are less than 1 A in nearly half of the cases and are greater than 2 A in only about one-third of them. Comparisons to published data on rms deviations show that Glide is nearly twice as accurate as GOLD and more than twice as accurate as FlexX for ligands having up to 20 rotatable bonds. Glide is also found to be more accurate than the recently described Surflex method.

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Crossref · 10.1021/jm0306430

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Authors
Friesner, R. A., Banks, J. L., Murphy, R. B., Halgren, T. A., Klicic, J. J., Mainz, D. T., Repasky, M. P., Knoll, E. H., Shelley, M., Perry, J. K., Shaw, D. E., Francis, P., & Shenkin, P. S.
Affiliations
D. E. Shaw Research (US)
Venue
Journal of Medicinal Chemistry
Published
2004-02-27
Volume
47
Issue
7
Pages
1739-1749
ISSN
  • 0022-2623 (ISSN-L)
  • 1520-4804
OpenAlex
W1985588649
Cited by
10,057
References
42
Citations by year
2026: 776 · 2025: 967 · 2024: 906 · 2023: 858 · 2022: 823 · 2021: 756 · 2020: 661 · 2019: 602 · 2018: 495 · 2017: 452 · 2016: 411 · 2015: 404 · 2014: 350 · 2013: 338 · 2012: 327
FWCI
85.86
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Medicinal Chemistry (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5p41rr006892-10)
  • National Institute of General Medical Sciences (GM52018, R01GM052018)
  • National Center for Research Resources (P41 RR 06892)
Topics
  • Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Physical Sciences › Physics and Astronomy › Atomic and Molecular Physics, and Optics › Advanced Chemical Physics Studies
Keywords
glides, molecular docking, docking accuracy, protein-ligand docking, protein-ligand complex, redocking, OPLS-AA force field, torsional flexibility, docking scoring functions, gold, FlexX, rotatable bonds
MeSH terms
Binding Sites, Ligands, Models, Molecular, Molecular Conformation, Monte Carlo Method, Protein Conformation, Proteins, Thermodynamics, Thymidine Kinase, Drug Design, Molecular Structure, Quantitative Structure-Activity Relationship

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