The extent to which the inherent structure of water is perturbed by complex molecules, such as proteins, peptides, and surfactants, influences the thermodynamics and the kinetics of their assembly. However, accurately characterizing this perturbation is challenging, because the manner in which proteins disrupt the inherent structure of water depends not only on the chemistry of the underlying protein surface, but also on the precise topographical and chemical pattern displayed by the protein. Nevertheless, understanding the role of water in protein interactions is essential to understanding, predicting, and eventually controlling such interactions, which play a crucial role in the development of therapeutic strategies and in protein separations.
In this presentation, I will discuss our recent successes in quantitatively characterizing the disruption of water structure in the hydration shell of proteins, and in using this information to predict the interfaces through which proteins interact with one another and self-assemble. Our approach also informs strategies for optimally modulating protein interactions, and facilitates the design of ligands that will bind to proteins of interest with high affinity and specificity. We hope that these advances will pave the way for the discovery of novel therapeutics that specifically target proteins of interest, and the rational design chromatographic ligands for challenging protein separations.