Lennard-Jones Potential and Dummy Atom Settings to Overcome the AUTODOCK Limitation in Treating Flexible Ring Systems
Abstract
Here, we present a setting-up procedure of AutoDock parameters that allows the management of cycle and macrocycle flexibility during the docking process. In particular, the glue dummy atom type is introduced into calculations, and a novel empirical pseudo-Lennard-Jones potential function is applied to describe the intramolecular interactions occurring between two glue dummy atoms. The reliability of such an original protocol is tested by evaluation of 21 cyclic ligands in the corresponding binding site. As a result, the binding mode of 17 ligands is well-reproduced with respect to the X-ray crystallographic structure, with an root-mean-square deviation lower than 2 Angstrom for 15 of them.
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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 [13]
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- Authors
- Forli, S., & Botta, M.
- Affiliations
- University of Siena (IT)
- Corresponding author
- Forli, Stefano
- Venue
- Journal of Chemical Information and Modeling
- Publisher
- American Chemical Society (ACS)
- Published
- 2007-06-22
- Volume
- 47
- Issue
- 4
- Pages
- 1481-1492
- ISSN
- 1549-9596 (ISSN-L)
- 1549-960X
- OpenAlex
- W2220752566
- Cited by
- 58
- References
- 12
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 3 · 2023: 2 · 2022: 9 · 2021: 4 · 2020: 6 · 2019: 8 · 2018: 1 · 2016: 3 · 2015: 4 · 2014: 2 · 2013: 2 · 2012: 4
- FWCI
- 1.17
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Chemical Information and Modeling (publishedVersion)
- PubMed (publishedVersion)
- Use Siena air (University of Siena) (submittedVersion)
- 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
- Lennard-Jones potential, AutoDock, macrocycle flexibility, cyclic ligands, molecular docking, intramolecular interactions, binding mode prediction
- MeSH terms
- Cyclization, Models, Molecular, Molecular Conformation, Crystallography, X-Ray
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