Effect of salts and organic additives on the solubility of proteins in aqueous solutions

The goal of this review is to examine the effect of salts and organic additives on the solubility of proteins in aqueous mixed solvents. The focus is on the correlation between the aqueous protein solubility and the osmotic second virial coefficient or the preferential binding parameter. First, several approaches which connect the solubility and the osmotic second virial coefficient are presented. Most of the experimental and theoretical results correlate the solubility and the osmotic second virial coefficient in the presence of salts. The correlation of the aqueous protein solubility with the osmotic second virial coefficient when the cosolvent is an organic component requires additional research. Second, the aqueous protein solubility is correlated with the preferential binding parameter on the basis of a theory developed by the authors of the present review. This theory can predict (i) the salting-in or -out effect of a cosolvent and (ii) the initial slope of the solubility curve. Good agreement was obtained between theoretical predictions and experimental results.