Glide: A new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy
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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A high docking score corresponds to more stable ligand-enzyme interactions and a low docking score suggests low binding affinity.
“As the docking score is the estimation of binding energy, the high docking score corresponds to more stable interactions between the ligand and the enzyme and low docking score suggests low binding affinity (Friesner et al., 2004).”
From Alpha-terpinyl acetate: A natural monoterpenoid from Elettaria cardamomum as multi-target directed ligand in Alzheimer’s disease (2020) · cites this paper as Friesner et al., 2004
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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
- Publisher
- American Chemical Society (ACS)
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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