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
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.