Abstract
Protein–protein interactions were measured for ovalbumin and for lysozyme in aqueous salt solutions. Protein–protein interactions are correlated with a proposed potential of mean force equal to the free energy to desolvate the protein surface that is made inaccessible to the solvent due to the protein–protein interaction. This energy is calculated from the surface free energy of the protein that is determined from protein–salt preferential‐interaction parameter measurements. In classical salting‐out behavior, the protein–salt preferential interaction is unfavorable. Because addition of salt raises the surface free energy of the protein according to the surface‐tension increment of the salt, protein–protein attraction increases, leading to a reduction in solubility. When the surface chemistry of proteins is altered by binding of a specific ion, salting‐in is observed when the interactions between (kosmotrope) ion–protein complexes are more repulsive than those between the uncomplexed proteins. However, salting‐out is observed when interactions between (chaotrope) ion–protein complexes are more attractive than those of the uncomplexed proteins. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 79: 367–380, 2002.