The Role of Water Molecules in Drug Design

Water widely exists in organisms and plays important roles in the interactions between drug molecules and target proteins. In drug design, replacement of water molecules and interactions with them are considered to be effective methods for lead optimization. In recent years, there have been a series of cases applying the method to improve the binding activity of compounds, enhance the selectivity, and optimize the pharmacokinetic properties. Through these cases, the method of replacing water molecules for lead optimization as well as the theories and software tools for studying the properties of water molecules are introduced with detailed discussion so as to provide some reference for lead optimization and innovative drug development.