Hydrophobicity and stability for a family of model proteins

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Abstract
According to the conventional definition, the hydrophobic effect is a result of thermodynamic changes occurring when a nonpolar group dissolves in water and attributable to the fact that water in contact with such a group has special structural and energetic properties. Disagreement now exists as to whether this effect promotes or hinders protein denaturation. Taking the heat capacity change of unfolding as a measure of the hydrophobicity of the protein interior, others have shown that protein stabilities are systematically affected by changes in hydrophobicity. It has been suggested that the observed trends show that hydrophobic hydration is intrinsically a destabilizing factor. Model calculations using known equations for the stability curves and certain simplifying assumptions now show that such regularities provide no evidence for or against this conclusion. All available data can be rationalized if hydrophobic terms are evaluated from models that require a positive hydrophobic contribution to the Gibbs energy of unfolding. The calculations also confirm the recent finding that any set of proteins with denaturation temperatures between about 330 and 380 K that exhibits entropy convergence at about 386 K is thermodynamically required to show enthalpy convergence at approximately the same temperature. © 1993 John Wiley & Sons, Inc.