The Advances and Limitations of the Determination and Applications of Water Structure in Molecular Engineering

Water is a key actor of various processes of nature and, therefore, molecular engineering has to take the structural and energetic consequences of hydration into account. While the present review focuses on the target–ligand interactions in drug design, with a focus on biomolecules, these methods and applications can be easily adapted to other fields of the molecular engineering of molecular complexes, including solid hydrates. The review starts with the problems and solutions of the determination of water structures. The experimental approaches and theoretical calculations are summarized, including conceptual classifications. The implementations and applications of water models are featured for the calculation of the binding thermodynamics and computational ligand docking. It is concluded that theoretical approaches not only reproduce or complete experimental water structures, but also provide key information on the contribution of individual water molecules and are indispensable tools in molecular engineering.