Effect of pH on phase separation of globular protein

Abstract

A molecular-thermodynamic framework is proposed to describe protein precipitation by inorganic salt. The equation of state consists of a hard-sphere reference contribution and a perturbation term. The reference term is derived based on the modified Chiew's model to describe the pre-aggregation effect of protein at various solution pH. In this study, we discuss protein-protein effective two-body potentials. The distribution and magnitude of charges on the surface of a protein vary significantly with pH. It changes the magnitude of charge-charge repulsion, charge-dipole attraction, dipole-dipole attraction, and induced dipole-induced dipole attraction forces between protein pairs in solution. The distribution of the charge fluctuation is slightly effective in solution pH. To investigate the effect of pH, modified charge fluctuation distribution model is proposed. Using the proposed model, we successfully describe the pH dependence of the protein precipitation.