Proteins water structure role

Scheidig, A. J., Burmester, C., and Goody, R. S. (1999). The pre-hydrolysis state of p21 (ras) in complex with GTP New insights into the role of water molecules in the GTP hydrolysis reaction of ras-like proteins. Structure 7, 1311-1324. 

In this article we shall examine the main achievements of microcalorimetric studies of protein denaturation and of the dissolution of nonpolar substances in water. This analysis has led us to reconsider the popular point of view on the mechanism of hydrophobic interaction and its role in the stabilization of protein structures. 

It was suggested earlier that hydrogen bonds in proteins are the main contributors to the denaturation enthalpy at 7X, whereas the nonpolar contacts determine only the temperature dependence of the denaturation enthalpy (Privalov, 1979). The main argument for this was the observation that proteins that have the same enthalpies at Tx have an almost equal concentration of intramolecular hydrogen bonds, but differ in the concentration of nonpolar contacts (Table I). As is evident, the assumption of the dominant role of hydrogen bonds in the stabilization of protein structure explained the observed temperature convergence of the denaturation enthalpy, if the enthalpy of exposure of nonpolar groups to water is zero at this temperature. This assumption implied that either the enthalpy of... 

One limitation to life at higher temperatures comes from the roles played by water in stabilizing the higher orders of protein structure. Hydrophobic interactions seem likely to be pivotal in this regard. Because hydrophobic sta-... 

Despite the fact that nonpolar hydration forces dominate whenever hydrophobic interactions [46] are important, the general availability of accurate models for the nonpolar component of the hydration-free energy is lacking. The structure and properties of proteins in water is highly influenced by hydrophobic interactions [47-50]. Hydrophobic interactions also play a key role in the mechanism of ligand binding to proteins [30,51-53], Empirical surface area models [54] for the nonpolar component of the solvation free energy are widely used [28,37,55-62]. Surface area models are useful as a first... 

Often, all the water is removed from the target protein structures prior to analysis. However, water molecules may play an important role in the enzyme and may be considered constitutive of the protein structure. In such cases, the final results and the success of the method may depend on keeping certain water molecules in the protein structure. The decision, which water molecules should be kept, depends mainly on external hints, such as a high occupancy and a low temperature factor in the crystallographic refinement or previous knowledge about its function in the protein. 

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