Quantifying the Hydrophobicity of Protein Surfaces At the Nano-Scale: A New Perspective

Traditionally, protein surfaces are characterized as hydrophobic or hydrophilic, based on the nature of the underlying amino-acids, by using hydropathy scales. Recent work has highlighted that the problem of characterizing hydrophobicity at the nano-scale is far more challenging. Water-mediated interactions are often non-additive in nature, and the hydrophobicity of a surface depends not only on the nature of the underlying groups, but also on the nature of the surrounding moieties and the surface topography. Proteins present surfaces that are both heterogeneous and structured to the surrounding water, thereby making it challenging to characterize them. Using molecular simulations, we propose a novel method to quantify the context-dependent hydrophobicity of a protein surface. Specifically, we quantify the ease with which water can be displaced from the hydration shell of the protein surface. In addition to being consistent with macroscopic notions of hydrophobicity, such as the contact angle, for a flat surface, our method is generally applicable, and can be used to characterize the hydrophobicity of nano-structured and heterogeneous surface, such as those of proteins and nanotubes.