(308d) Painting Protein Surfaces with a Nanoscale Paint-Brush: Hydration, Fluctuations, and Interactions of Proteins in Solution

Binding of proteins to ligands or protein-protein interactions in solution are influenced by the pattern of hydrophobicity or hydrophilicity on a protein surface. Macroscopically, hydrophobicity/philicity of a surface is frequently characterized by droplet contact angle measurements, which are not feasible for nanoscopic and submerged interfaces of proteins, ligands, or other nanoscale objects. Recently, our group has demonstrated that fluctuations of water density, water-water correlations, or the propensity of binding probe hydrophobic solutes to a given site provide excellent molecular measures of hydrophobicity of complex ? rough and chemically heterogeneous ? surfaces of proteins. Using extensive simulations of several proteins we demonstrate that this new molecular approach presents a powerful nanoscale paint-brush that accounts for the behavior of hydration water within a chemical and topographical context of the protein surface. Our results highlight the limitations of context-independent hydropathy scales that are frequently used in biochemistry and physics. A broader application of this new method has the potential to help understand and predict binding free energies and preferences of proteins, to improve drug design by taking into account the behavior of hydration water, and to functionally annotate proteins.