Temperature dependence of the hydrophobic interaction in protein folding.

Abstract

Accurate calorimetric data for the thermodynamics of transfer of six liquid hydrocarbons to water have been combined with solubility data to provide a model for the temperature dependence of the hydrophobic interaction in protein folding. The model applies at temperatures for which the change in heat capacity (delta Cp) is constant. The extrapolated value of the temperature (Ts) at which the entropy of transfer (delta S degrees) reaches zero is strikingly similar (Ts = 112.8 degrees C +/- 2.2 degrees C) for the six hydrocarbons. This finding provides an interpretation for the empirical relation discovered by Sturtevant: the ratio delta S degrees/delta Cp measured at 25 degrees C is constant for the transfer of nonpolar substances from nonaqueous media to water. Constancy of this ratio is equivalent to Ts = constant. When applied to protein folding, the hydrocarbon model gives estimates of the contributions of the hydrophobic interaction to the entropy and enthalpy changes on unfolding and, by difference, estimates of the residual contributions from other sources. The major share of the large enthalpy change observed on unfolding at high temperatures comes from the hydrophobic interaction. The hydrophobic interaction changes from being entropy-driven at 22 degrees C to being enthalpy-driven at 113 degrees C. Finally, the hydrocarbon model predicts that plots of the specific entropy change on unfolding versus temperature should nearly intersect close to 113 degrees C, as observed by Privalov.