title: Water in cavity-ligand recognition.
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.
authors.affiliation: Department 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
authors.forename: Riccardo
authors.initials: R
authors.lastname: Baron
authors.forename: Piotr
authors.initials: P
authors.lastname: Setny
authors.forename: J Andrew
authors.initials: JA
authors.lastname: McCammon
mesh_terms: D008024:Ligands; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D011506:Proteins / Q000737:chemistry; D013816:Thermodynamics; D014867:Water / Q000737:chemistry*
chemical_list: D008024:Ligands; D011506:Proteins; D014867:Water