ON THE ORIGIN OF THE ENTHALPY AND ENTROPY CONVERGENCE TEMPERATURES IN PROTEIN FOLDING

Temperature dependence of the thermodynamics of folding/unfolding for cytochrome c has been determined as a function of moderate [0-10% (vol/vol)] concentrations of methanol. Heat capacity change (DELTAC(p)) for unfolding decreases with increased concentrations of methanol, consistent with a higher solvent hydrophobicity. For a given transition temperature, this effect results in higher experimental enthalpy (DELTAH and entropy (DELTAS) changes with increased methanol concentrations. When the enthalpy or entropy data sets obtained at different methanol concentrations are plotted as a function of temperature, they are seen to converge and assume common values around 100-degrees-C for DELTAH and 112-degrees-C for DELTAS. These convergence temperatures are similar to those obtained for different proteins in aqueous solution when DELTAH and DELTAS are normalized with respect to number of residues. It has been previously hypothesized that these convergence temperatures correspond to the temperatures at which the hydrophobic contributions to DELTAH and DELTAS are zero; the results presented here agree with this viewpoint.