VANT HOFF REVISITED - ENTHALPY OF ASSOCIATION OF PROTEIN SUBUNITS

The amounts of heat absorbed from and released to the environment in a chemical reaction are not experimentally separable. In consequence, entropy and enthalpy of reaction can only be computed with the help of specific hypotheses that relate them. We adopt here a previously described model in which enthalpy and entropy changes on reaction are determined by the thermally dependent probability of bond breakage, and we derive a simple function of that probability that gives the number of Boltzmann complexions associated to a set of bonds of arbitrary strength. The general relation proposed by Born for the dependence of bond energy upon distance is used to demonstrate that increase in pressure from atmospheric to 2.5 kbar produces much larger dissociating effects than increase in temperature from 0 to 40 degrees C. In protein oligomers the energies of protein-protein bonds are of the same order as the thermal energy, and both enthalpy and entropy of reaction must undergo significant;changes with temperature. The ''van't Hoff enthalpies'', which are calculated on the assumption that enthalpy and entropy are constants independent of temperature, correspond to not one but two very different values of the enthalpies predicted by the model, but the effects of pressure upon the reaction can be used to choose between them. Application of these procedures to seven oligomeric proteins previously studied shows that the enthalpies so determined are remarkably alike with a mean value of +25 +/- 5 kcal per 1000 Angstrom(2) of intersubunit surface, as compared with +7 +/- 6 kcal derived for the corresponding van't Hoff enthalpies.