Water: Active or Passive Player in Cavity-Ligand Recognition & Binding?

Dr. Riccardo Baron
Department of Chemistry and Biochmistry and Center for Theoretical Biological Physics
UC San Diego


ABSTRACT


We use a straightforward approach based on potential of mean force calculations from explicit solvent molecular dynamics simulations to derive complete thermodynamic signatures of cavity-ligand binding. Using extensive sampling, free energy, enthalpy, and entropy estimates are obtained along the binding coordinate for a set of systems with varying cavity and ligand physicochemical properties, thus revealing an unprecedented, nanoscale picture of hydration thermodynamics. Despite the simplicity of the model systems considered, a broad range of thermodynamic signatures is found in which water (rather then cavity or ligand) contributions appear to largely determine the overall system enthalpy-entropy compensation.