Theoretic information approach to protein stabilization by solvent engineering

Abstract

AbstractA novel approach based on molecular thermodynamics and the information theory is proposed to quantify the influence of water‐miscible additives on protein stability. According to the two‐state mechanism of inactivation, solvent effects are described in terms of perturbation of the equilibrium between the folded and unfolded protein forms. The model provides the dependence of the protein's melting temperature on the additive concentration. Effects of the latter are accounted for by an empirical parameter related to the free energy of transfer of the protein from the pure to the mixed solvent. The model was tested using experimental data relative to the influence of hydroxylic and aminoacidic additives on the thermal unfolding of hen egg lysozyme and erythrocyte carbonic anhydrase. Fitting parameters were correlated in terms of a theoretic information index characterizing the additive's molecule and incorporating an atomic‐composition term and a topological contribution. Model calculations agreed very well with experimental data, suggesting that the molecular information content of the additive can be used effectively to correlate solvent‐induced perturbations of stability. The procedure was also used to predict melting temperatures in systems containing binary mixtures of additives and to reconstruct thermal unfolding curves in the different media.