Understanding Protein Hydration to Inform Its Interactions and Assemblies

The interactions of a protein surface with water, that is, its hydrophobicity dictates the interactions of the protein with ligands, other proteins, and extended interfaces. However, the hydrophobicity of a complex, heterogeneous protein surface depends, not only on the chemistry of the underlying amino acids, but also on the precise chemical pattern and topographical context presented by the protein surface. Methods for accurately and efficiently characterizing the context-dependent hydrophobicity of protein surfaces will presented. Further, how such estimates of protein hydrophobicity can be used to estimate interactions between two such protein surfaces will be discussed. Finally, the use of this framework to determine protein hydration free energies and interaction interfaces will be demonstrated.