SOLVENT ISOTOPE EFFECT AND PROTEIN STABILITY

Here we present a comparative study of the stability of several protei ns in H2O and D2O as a function of pH/pH. We show that the substituti on of D2O for H2O leads to an increase in the transition temperature a nd a decrease in the enthalpy of unfolding. The stability of the prote ins, however, appears to be largely unchanged as a result of entropic compensation for the decrease in enthalpy. This enthalpy-entropy compe nsation is attributed to changes in hydration of proteins in D2O compa red to-H2O. Analysis of thermodynamic data for the transfer of model c ompounds from H2O to D2O shows that almost all the changes in the enth alpy of unfolding and in the protein-ligand interactions due to water isotopic substitution can be rationalized by changes in hydration of t he buried non-polar groups.