The Role of Water Network Chemistry in Proteins: A Structural Bioinformatics Perspective in Drug Discovery and Development

Abstract

Background: Although water is regarded as a simple molecule, its ability to create hydrogen bonds makes it a highly complex molecule that is crucial to molecular biology. Water mo-lecules are extremely small and are made up of two different types of atoms, each of which plays a particular role in biological processes. Despite substantial research, understanding the hydration chemistry of protein-ligand complexes remains difficult. Researchers are working on harnessing water molecules to solve unsolved challenges due to the development of computer technologies. Objective: The goal of this review is to highlight the relevance of water molecules in protein envi-ronments, as well as to demonstrate how the lack of well-resolved crystal structures of proteins fun-ctions as a bottleneck in developing molecules that target critical therapeutic targets. In addition, the purpose of this article is to provide a common platform for researchers to consider numerous as-pects connected to water molecules. Conclusion: Considering structure-based drug design, this review will make readers aware of the different aspects related to water molecules. It will provide an amalgamation of information related to the protein environment, linking the thermodynamic fingerprints of water with key therapeutic targets. It also demonstrates that a large number of computational tools are available to study the water network chemistry with the surrounding protein environment. It also emphasizes the need for computational methods in addressing gaps left by a poorly resolved crystallized protein structure.