PREDICTION AND STRUCTURAL-ANALYSIS OF THE ENTHALPY OF IONIZATION OF PROTEINS

A theoretical model is proposed for the prediction and analysis of the acid-base calorimetric titration of proteins. The model is based on t he inclusion of the additive calorimetric contributions in a semi-empi rical electrostatic method. Any electrostatic approach predicting pK(a ) values can be used for the analysis of calorimetric titration curves . The first step in the treatment is to find relationships between the ionization enthalpies of titratable amino acid residues and the relat ive solvent accessibilities of their ionizing atoms (AA(i)). This is a chieved on the basis of relations between the experimental values of e nthalpies of the ionization of appropriate model compounds in aqueous organic solutions and their dielectric permeabilities. The predicted c alorimetric titration curves of myoglobin, cytochrome c, ribonuclease A, lysozyme and alpha-chymotrypsin are compared with the available exp erimental data. Our results describe qualitatively the calorimetric ti tration of the first four proteins, while assuming a possible artifact in an experimental lysozyme calorimetric titration and predict the ti tration curve of alpha-chymotrypsin. This paper also presents the deve lopment of an analysis of the differential calorimetric titration curv es, which can describe the contributions of individual ionizable group s. Such an analysis is demonstrated for the case of ferri- or ferro-cy tochrome c as an example. (C) 1997 Elsevier Science B.V.