EVALUATION OF "FREE ENERGY" FOR NON-COVALENT INTERACTIONS IN PROTEIN STRUCTURES

For a large number of protein it has now been stablishcd that their na-tives structures are thermodynamically stable (Santoro & Bolen, 1988) (The thermodynamic hipothesis (Anfinsen, 1973)). Thus in these proteins the native structure corresponds, by definition, to the macroscopic state having a global minimum of th free energy relative to all other states acces-sible on that time scale (Dill, 1990). The free energy of a protein structure consists of the sum of contributions from its intramolecular interactions and from the interaction of the molecule with the surrounding solvent wa-ter. Exact computation of those contributions sitll poses problems specia-lly when effects with a strong entropic component, such as the hydropho-bic forces or the conformational entropy, have to be evaluated (Ooi et al., 1987). Thus the accurate modeling of protein folding processes appears still as a distant goal (Karplus & Pctsko, 1990). There are different approaches to evaluate the interactions of a mole-cule with its surrounding solvent (Finney & Savage, 1988; Warshel & Creighton, 1989), in particular, it has been proposed (Eisenberg & McLa-chlan, 1986; Ooi et al., 1987) that the extent of the interaction of any func-tional group i of the solute with the solvent is proportional to the solvent-accessible surface area Si ° (Lee & Richards, 1971; Richards, 1977) of group i. The total free energy of hydration of a solute molecule is then expressed as