Work

Water in Cavity−Ligand Recognition

Year: 2010

Type: article

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.

Source: Journal of the American Chemical Society

DOI: 10.1021/ja1050082

Authors: Riccardo Baron, Piotr Setny, J. Andrew McCammon

Institutions: Howard Hughes Medical Institute, University of California San Diego, Center for Theoretical Biological Physics, Technical University of Munich

Language: English

Topic: Supramolecular Chemistry and Complexes

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: hybrid

Estimated APC paid: $4,500

Funders: National Science Foundation, Howard Hughes Medical Institute, National Institutes of Health, Center for Theoretical Biological Physics