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Updated: Jun 10, 2026
Modeling Ligands into Maps Derived from Electron Cryomicroscopy
Published on: July 19, 2024
Water in cavity-ligand recognition
Riccardo Baron1, Piotr Setny, J Andrew McCammon
1Department of Chemistry and Biochemistry, Center for Theoretical Biological Physics, Howard Hughes Medical Institute, University of California, San Diego, California 92093, USA. rbaron@mccammon.ucsd.edu
Abstract:
We use explicit solvent molecular dynamics simulations to estimate free energy, enthalpy, and entropy changes along the cavity-ligand association coordinate for a set of seven model systems with varying physicochemical properties. Owing to the simplicity of the considered systems we can directly investigate the role of water thermodynamics in molecular recognition. A broad range of thermodynamic signatures is found in which water (rather than cavity or ligand) enthalpic or entropic contributions appear to drive cavity-ligand binding or rejection. The unprecedented, nanoscale picture of hydration thermodynamics can help the interpretation and design of protein-ligand binding experiments. Our study opens appealing perspectives to tackle the challenge of solvent entropy estimation in complex systems and for improving molecular simulation models.
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