Approaches to efficiently estimate solvation and explicit water energetics in ligand binding: the use of WaterMap.
Abstract
INTRODUCTION: Water displacement plays critical role in several phases of drug discovery. Proper treatment of displacing water could improve enrichment in virtual screening and could lead to more successes in lead optimization. WaterMap has recently emerged as a promising approach in this regard; recent implementations of this protocol successfully explained various binding activity that were poorly understood previously, including the well-known super affinity associated with biotin binding to streptavidin. AREAS COVERED: The review briefly discusses implicit and explicit solvent models and focuses on an application of inhomogeneous solvation theory - WaterMap. Furthermore, the review discusses various successful cases where the use of WaterMap explained selectivity in protein-ligand binding and provides discussion of the fundamentals and recently successful implementations of WaterMap. The authors also discuss the limitations of this protocol and list a few approaches that could extend its implementation to more cases. EXPERT OPINION: WaterMap is a powerful tool for calculating the cost of desolvation for structural waters. In some cases, it proved useful in predicting relative binding free energy differences for congeneric ligands. The practical utility of WaterMap hinges in adequate application of the results in the context of all the thermodynamic contributions to binding. Potential improvements as well as integration into methods such like MM-GB/SA could extend its success.
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A water-mapping protocol based on post-trajectory analysis of explicit solvent MD uses inhomogeneous solvation theory and tries to predict the free energy cost of moving a water molecule from a protein hydration site into the bulk solvent.
“An interesting approach is the use of a water-mapping protocol based on the post trajectory analysis of explicit solvent MD. This analysis is based on the inhomogeneous solvation theory and tries to predict the free energy cost of moving a water molecule from a protein hydration site into the bulk solvent (Yang et al., 2013).”
From Empirical scoring functions for structure-based virtual screening: applications, critical aspects, and challenges (2018) · cites this paper as Yang et al., 2013
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- Authors
- Yang, Y., Lightstone, F. C., & Wong, S. E.
- Affiliations
- Lawrence Livermore National Laboratory (US)
- Venue
- Expert Opinion on Drug Discovery
- Publisher
- Informa UK Limited
- Published
- 2013-01-04
- Volume
- 8
- Issue
- 3
- Pages
- 277-287
- ISSN
- 1746-0441 (ISSN-L)
- 1746-045X
- OpenAlex
- W2008870093
- Cited by
- 65
- References
- 96
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 3 · 2023: 7 · 2022: 7 · 2021: 2 · 2020: 5 · 2019: 3 · 2018: 4 · 2017: 5 · 2016: 3 · 2015: 9 · 2014: 5 · 2013: 4
- FWCI
- 0.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Expert Opinion on Drug Discovery (publishedVersion)
- PubMed (publishedVersion)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- Topics
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
- Physical Sciences › Physics and Astronomy › Atomic and Molecular Physics, and Optics › Advanced Chemical Physics Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- solvation energy, structural water, protein-ligand binding, desolvation, binding free energy, virtual screening, biotin-streptavidin binding, binding selectivity, MM-GBSA, implicit solvent
- MeSH terms
- Ligands, Models, Molecular, Protein Binding, Solvents, Water
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