Salt-induced protein precipitation in aqueous solution: The effect of pre-aggregation

Abstract

A molecular-thermodynamic model is developed for the salt-induced protein precipitation. The protein molecules interact through four intermolecular potentials. An equation of state is derived based on the statistical mechanical perturbation theory with the modified Chiew’s equation as the reference system and a perturbation based on the protein-protein interaction potential of mean force. The equation of state provides an expression for the chemical potential of the protein and determines liquid-liquid equilibria. The precipitation behaviors are studied by calculating the partition coefficient with changing conditions such as ionic strength, protein and salt size, and the degree of pre-aggregation effect. The reasonable pre-aggregation effects are determined by comparing the proposed model with experimental data.