The enthalpy of transfer of unfolded proteins into solutions of urea and guanidinium chloride.

G. Makhatadze and P. Privalov [J. Mol. Biol., 226 (1995) 491] have recently measured the enthalpy of transfer of three proteins into urea and guanidinium chloride solutions as a function of concentration and temperature. The present paper applies the solvent-exchange model [J.A. Schellman, Biopolymers, (1994)] to the data and compares it with the binding model utilized in the original publication. Both calculations assume identical binding sites. It is found that the data may be fit tolerably well using either procedure, but that the parameters describing the binding vary considerably. Consideration of the transfer properties of amino acid moieties and small peptides leads to the conclusion that solvation sites are heterogeneous and that the quantities determined by both methods are statistical averages. The parameters describe an identical-site system that has (approximately) the same properties as the real heterogeneous system. The results have mainly heuristic and mechanistic value. One quantity determined with these simplified isotherms, sigma kj delta hj, is a property of the real system and can serve as a measure of a thermal binding capacity for a protein. The appendices contain a resume of the solution theory required for the exchange model of solvation as well as the development of a number of empirical equations for the thermodynamic properties of urea and guanidinium chloride solutions.