The role of water in ligand binding

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.

Automated summary

This review discusses recent advancements in understanding the modulatory role of water in ligand-target binding in drug design. Theoretical approaches have shown remarkable progress, providing immeasurable data and improving ligand binding through thermodynamic calculations and selection of water molecules for structural replacement. Molecular dynamics and explicit solvent models are essential for achieving precise results, and topographical analyses of hydration networks are useful for predicting the stabilizing role of interconnected water clusters mediating target-ligand interactions.