Protein flexibility in drug discovery: from theory to computation.
Abstract
Nowadays it is widely accepted that the mechanisms of biomolecular recognition are strongly coupled to the intrinsic dynamic of proteins. In past years, this evidence has prompted the development of theoretical models of recognition able to describe ligand binding assisted by protein conformational changes. On a different perspective, the need to take into account protein flexibility in structure-based drug discovery has stimulated the development of several and extremely diversified computational methods. Herein, on the basis of a parallel between the major recognition models and the simulation strategies used to account for protein flexibility in ligand binding, we sort out and describe the most innovative and promising implementations for structure-based drug discovery.
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Protein flexibility is still a great challenge for docking programs and scoring functions.
“Protein flexibility is still a great challenge for docking programs and scoring functions (Cavasotto and Singh, 2008; Tuffery and Derreumaux, 2012; Buonfiglio et al., 2015; Spyrakis and Cavasotto, 2015; Kurkcuoglu et al., 2018).”
From Empirical scoring functions for structure-based virtual screening: applications, critical aspects, and challenges (2018) · cites this paper as Buonfiglio et al., 2015
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- Authors
- Buonfiglio, R., Recanatini, M., & Masetti, M.
- Affiliations
- AstraZeneca (Sweden) (SE)
- University of Bologna (IT)
- Corresponding author
- Masetti, Matteo
- Venue
- ChemMedChem
- Publisher
- Wiley
- Published
- 2015-04-17
- Volume
- 10
- Issue
- 7
- Pages
- 1141-1148
- ISSN
- 1860-7179 (ISSN-L)
- 1860-7187
- OpenAlex
- W2058181174
- Cited by
- 73
- References
- 77
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 7 · 2023: 4 · 2022: 17 · 2021: 4 · 2020: 5 · 2019: 8 · 2018: 10 · 2017: 8 · 2016: 1 · 2015: 2
- FWCI
- 0.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- ChemMedChem (publishedVersion)
- PubMed (publishedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Interaction Studies and Fluorescence Analysis
- Keywords
- protein flexibility, protein conformational dynamics, ligand binding, biomolecular recognition, structure-based drug design
- MeSH terms
- Ligands, Molecular Conformation, Proteins, Drug Discovery, Molecular Dynamics Simulation
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