A theoretical approach to predict the solubility of proteins in solutions containing nonionic polymer is presented. The effective protein-protein interaction due to the presence of the polymer is related to the volume-exclusion potential of Asakura and Oosawa. Statisticalmechanical perturbation theory, as originally applied by Gast et al. to model colloidal flocculation, is used to calculate free energies, from which solubility curves for varying protein-polymer diameter ratios are obtained. The theory correctly predicts all the trends observed in experimental studies of these systems. To explain the influence of process parameters such as the pH and the ionic strength on protein solubility, the intermolecular potential is improved by the addition of an electrostatic interaction term. It is found that the theoretical predictions of the variation in protein solubility, both with the solution pH and the ionic strength, are in accordance with experimental observations. precipitated protein fraction (Bjurstrom, 1985;Scopes, 1982).However, it has been found that using PEG of a higher average molecular weight significantly reduces the contamination of the

A theory is developed to predict the solubility of protein mixtures in solutions containing nonionic polymer. Effective protein-protein interactions due to polymer are taken to be volume-exclusion potentials derived using statistical mechanics. Statistical-mechanical perturbation theory is used to calculate chemical potentials. The effects of protein size, mole fraction and polymer concentration on solubility are explored. The theory is extended to include electrostatic interactions. The excess chemical potential of the proteins due to the charges on all species is calculated using the mean spherical approximation for a mixture of charged hard spheres. The theory predicts: the larger protein is preferentially precipitated over the smaller one; the more concentratedprotein is more likely to precipitate; and increasing the charge of a particular protein reduces its ability to precipitate.

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