We present a simplified model describing liquid water which explains the temperature-dependent free energy of interfacial H-bonds and the hydrophobic effect. Water is represented as a network consisting of nodes with four H-bond functions which are either satisfied or unsatisfied. Temperature dependent fractions of satisfied and unsatisfied H-bond functions as well as the free energy of H-bonds in water were derived using a thermodynamic cycle. In addition, we have deduced (de)hydration terms for polar and apolar groups (e.g. in proteins or ligands) which predict the contributions of interfacial H-bonds and the hydrophobic effect in good agreement with experiments.This concept is the basis of our scoring function named HYDE which estimates the binding free energy of protein-ligand complexes. Very satisfying results were obtained with HYDE on public benchmark datasets in the discrimination of binders and non-binders for different protein targets and in predicting the bioactive conformation of a ligand.

Impact of unsatisfied H-bond functions on intermolecular interactions in water

243rd National Meeting (2012)

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