  The interactions of a protein, its phase behavior, and ultimately, its
ability to function, are all influenced by the interactions between the protein
and its hydration waters. Here we study proteins with a variety of sizes,
shapes, chemistries, and biological functions, and characterize their
interactions with their hydration waters using molecular simulation and
enhanced sampling techniques. We find that akin to extended hydrophobic
surfaces, proteins situate their hydration waters at the edge of a dewetting
transition, making them susceptible to unfavorable perturbations. We also find
that the strength of the unfavorable potential needed to trigger dewetting is
roughly the same, regardless of the protein being studied, and depends only the
width of the hydration shell being perturbed. Our findings establish a
framework for systematically classifying protein patches according to how
favorably they interact with water.
