Executive Summary : | Hydration water plays a pivotal role in the aggregation of intrinsically disordered proteins both in vivo and in vitro. The contributions of the protein-water interactions have been demonstrated by analyzing the effect of point mutations on the aggregation propensity of disordered proteins. Protein aggregation in cellular environments is implicated in various neurodegenerative disorders, diabetes, cardiovascular problems and some forms of cancer. The aggregation propensity of a monomeric protein depends on its characteristic affinity towards water. The synergistic relationship between any protein and water is particularly significant for the disordered proteins due to their increased solvent-accessible surface area as compared to the globular proteins. The changes in the local structure and dynamics of hydration water molecules characterize these protein-water interactions. This project proposes to investigate the effect of point/pair mutations on the hydration environment and aggregation propensity of disordered proteins to facilitate the design of aggregation-resistant proteins for combating these diseases. |