THERMODYNAMICS OF THE ASSOCIATION AND THE PRESSURE DISSOCIATION OF OLIGOMERIC PROTEINS

A relation giving the distribution of the energies and the entropy of a set of identical bonds as a function of a suitably defined bond strength E is derived. The resulting normal distributions have energies that increase monotonically with E and entropies with a maximum at E/RT = In 2 and almost negligible values at E/RT > 5-7. Association of two protein subunits involves conversion of two sets of protein-water bonds (P-W) into separate water-water (W-W) and protein-protein (P-P) sets, and the constant W-W bond strength permits the determination of the P-P and P-W bond strengths from the experimental enthalpies and entropies of subunit association. Data on the dissociation of four dimers, one trimer, and two tetramers by hydrostatic pressure give E(p-p) = 1.8 +/- 0.8 kcal and E(P-W) = 4.4 +/- 0.5 kcal. In contrast to prevalent views, the large entropy increase that drives these associations results from the conversion of the stronger P-W bonds into the weaker P-P bonds, while the conversion of P-W into W-W bonds does not make any appreciable contribution to it. The effects of temperature and pressure on the bond energies may be computed from the intermolecular potentials typical of dipolar and apolar interactions and by specification of the proportions of each type in the P-P and P-W bonds. The dissociating effect of pressure and the temperature stabilization of protein aggregates follow from the differential expansivities and compressibilities associated to the different bond strengths.