Estimation of steric exclusion and differential interaction contributions to protein transfer free energies in aqueous cosolvent solutions

The thermal stability, conformation and aggregation of globular proteins depend on the concentration and type of cosolvents present in the surrounding aqueous phase. The transfer free energy of proteins into cosolvent solutions provides a quantitative description of the influence of cosolvents on protein transitions between different states, e.g. folded vs. unfolded or aggregated vs. non-aggregated. An improved understanding of the physiochemical processes contributing to transfer free energies would facilitate the rational utilization of proteins as functional ingredients in compositionally complex foods. This paper describes a thermodynamic model for predicting steric exclusion and differential interaction (protein-dependent and protein-independent) contributions to protein transfer free energies in cosolvent solutions. The usefulness and limitations of the model are demonstrated by analyzing published protein transfer free energies.