Epistructural Dynamics of Biological Water

Abstract

Adopting the methods of epistructural physics previously developed, this chapter unravels dynamic singularities of the protein-water interface. It is shown that interfacial water in the vicinity of protein dehydrons is subject to a torque resulting from the breakdown of the Debye dielectric picture. This non-Debye torque accelerates interfacial water molecules beyond the kinetic energies characteristic of the bulk. The epistructural dynamic analysis highlights a link between the protein structural deficiencies and the defects of the aqueous interface. Thus, the tightness of the hydration shell is modulated by the mobility of interfacial water that varies widely becoming a maximum at dehydron locations. Interfacial water molecules subject to the non-Debye torque enhance the propensity for protein associations and raise their catalytic rate as proton acceptors by increasing the frequency of effective collisions. The most pronounced de-wetting propensity at the interface is promoted by dehydrons on the surface of soluble proteins. The result has crucial implications for the drug designer since ligands may be engineered to expel labile interfacial patches upon association. Furthermore, subtle differences in the interfacial dynamic singularities within a protein family may be exploited to promote drug specificity. This finding is of significance to the pharmaceutical industry since homologous proteins are known to share a common structural topology and therefore, discriminatory molecular recognition remains a daunting challenge.