CORRELATION BETWEEN NATIVE-STATE HYDROGEN-EXCHANGE AND COOPERATIVE RESIDUE FLUCTUATIONS FROM A SIMPLE-MODEL

Recently, we developed a simple analytical model based on local residu e packing densities and the distribution of tertiary contacts for desc ribing the conformational fluctuations of proteins in their folded sta te. This so-called Gaussian network model (GNM) is applied here to the interpretation of experimental hydrogen exchange (HX) behavior of pro teins in their native state or under weakly denaturing conditions. Cal culations are performed for five proteins: bovine pancreatic trypsin i nhibitor, cytochrome c, plastocyanin, staphylococcal nuclease, and rib onuclease H. The results are significant in two respects, First, a goo d agreement is reached between calculated fluctuations and experimenta l measurements of HX despite the simplicity of the model and within co mputational times 2 or 3 orders of magnitude faster than earlier, more complex simulations. Second, the success of a theory, based on the co upled conformational fluctuations of residues near the native state, t o satisfactorily describe the native-state HX behavior indicates the s ignificant contribution of local, but cooperative, fluctuations to pro tein conformational dynamics. The correlation between the HX data and the unfolding kinetics of individual residues further suggests that lo cal conformational susceptibilities as revealed by the GNM approach ma y have implications relevant to the global dynamics of proteins.