This chapter examines the hydration patterns of soluble proteins to unravel the dynamic singularities of the protein–water interface. It is shown that dehydrons “heat up” interfacial water, thereby highlighting a link between wrapping deficiencies and defects in the hydration shell. The emerging picture is that biomolecular interfaces are dynamic objects: their tightness, marked by the mobility of interfacial water, varies widely, is site-dependent, and modulates the propensity for protein associations. As shown, the most pronounced interfacial de-wetting propensity is promoted by stable dehydrons on the surface of soluble proteins. The result has crucial implications for the molecular designer as drugs may be engineered to expel the labile patches of the target hydration shell upon binding. Furthermore, subtle differences in the location of hydration defects in proteins within the same family may be exploited to enhance drug specificity. This finding is noteworthy since homologous proteins are known to share a common structure topology and therefore, telling them apart through molecular recognition becomes a particularly arduous problem.
Interfacial Water Hydration Shell Protein Association Nonpolar Group Mechanical Equivalent
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