Automated docking to multiple target structures: Incorporation of protein mobility and structural water heterogeneity in AutoDock
Abstract
Protein motion and heterogeneity of structural waters are approximated in ligand‐docking simulations, using an ensemble of protein structures. Four methods of combining multiple target structures within a single grid‐based lookup table of interaction energies are tested. The method is evaluated using complexes of 21 peptidomimetic inhibitors with human immunodeficiency virus type 1 (HIV‐1) protease. Several of these structures show motion of an arginine residue, which is essential for binding of large inhibitors. A structural water is also present in 20 of the structures, but it must be absent in the remaining one for proper binding. Mean and minimum methods perform poorly, but two weighted average methods permit consistent and accurate ligand docking, using a single grid representation of the target protein structures. Proteins 2002;46:34–40. © 2001 Wiley‐Liss, Inc.
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The specification and architecture of AutoDock was designed to allow user modification for specialized systems, and has been used previously to model protein flexibility, flexible rings in ligands, zinc interaction, and selective hydration.
“The specification and architecture of AutoDock was designed to allow this type of user modification for specialized systems, and has been used previously to model protein flexibility, 12 flexible rings in ligands, 13 zinc interaction, 14 and selective hydration.15”
From Covalent docking using autodock: two-point attractor and flexible side chain methods. (2016) · cites this paper as [12]
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- Authors
- Österberg, F., Morris, G. M., Sanner, M. F., Olson, A. J., & Goodsell, D. S.
- Affiliations
- Scripps Research Institute (US)
- Corresponding author
- Goodsell, David S.
- Venue
- Proteins: Structure, Function, and Bioinformatics
- Publisher
- Wiley
- Published
- 2001-11-15
- Volume
- 46
- Issue
- 1
- Pages
- 34-40
- ISSN
- 0887-3585 (ISSN-L)
- 1097-0134
- OpenAlex
- W2062378498
- Cited by
- 474
- References
- 19
- Citations by year
- 2026: 4 · 2025: 14 · 2024: 11 · 2023: 23 · 2022: 14 · 2021: 17 · 2020: 16 · 2019: 16 · 2018: 15 · 2017: 13 · 2016: 19 · 2015: 26 · 2014: 18 · 2013: 17 · 2012: 26
- FWCI
- 23.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Proteins Structure Function and Bioinformatics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (P01 GM48870)
- 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 › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Keywords
- AutoDock, protein-ligand docking, protein conformational ensembles, protein mobility, HIV-1 protease, peptidomimetic inhibitors
- MeSH terms
- Computer Simulation, Ligands, Motion, Protein Conformation, Proteins, Water, Pliability
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