The role of water in ligand binding
Balázs Zoltán Zsidó, Csaba Hetényi
Abstract
Exploration of the complex modulatory role of water in ligand–target binding is a current challenge of drug design. This review reports on recent advances of prediction of water structure and function in the context of ligand engineering. The surveyed theoretical approaches showed remarkable progress in the past years. Beyond complementing experiments, they also supplied unmeasurable data. For example, thermodynamic calculations improved ligand binding by the selection of certain water molecules for structural replacement. Molecular dynamics and explicit solvent models remained indispensable to achieve precise results. Topographical analyses of hydration networks proved useful for the prediction of the stabilizing role of interconnected water clusters mediating target–ligand interactions. • Computational prediction of water structure helps the optimization of drug binding. • Molecular dynamics is a key to thermodynamic selection of water molecules influencing target-ligand interactions. • Drug design will benefit from graph theoretical characterization of hydration networks.