Abstract
The conformational stability of a protein in an aqueous solution is described by the Gibbs free energy of unfolding between the native and random conformation.
The free energy of unfolding consists of two contributions: the hydration around the molecule, and the intramolecular interactions. A method to calculate the free energy of hydration from the accessible surface area (ASA) of the constituent atomic groups in a protein has been developed assuming a proportionality of the free energy to ASA. Similarly, the free energy of unfolding for the chain in vacuo can also be calculated from the ASA, using the unfolding thermodynamics derived from the experimental data of 10 proteins. Thus, our method can predict the unfolding thermodynamics of a protein with a known tertiary structure. The predicted values of 4 other proteins agreed well with the experimentally derived values. This method also accounted for the temperature dependences of the free energy of unfolding and the enthalpy changes of T4 lysozyme, and the occurrence of cold denaturation at a low temperature. This method was applied to the unfolding thermodynamics of the poly (L-alanine) helix. The calculated enthalpy change is close to the value determined in a recent calorimetric study of a 50-residue alanine-rich helix, and the results suggest that helix formation is enthalpy-driven.
