A molecular-thermodynamic model is developed for salt-induced protein
precipitation, which considers an aqueous solution of globular protein
molecules as a pseudo-one-component system containing macroions that
interact through Coulombic repulsion, dispersion attraction and hydrop
hobic interactions and forces arising from ion-excluded volume. Forces
from ion-excluded volume rake into account formation of ion pairs and
ionic clusters at high salt concentrations; they are calculated in th
e context of the Percus-Yevick integral-equation theory. Hydrophobic i
nteractions between exposed nonpolar amino-acid residues on the surfac
es of the protein molecules are modeled as short-range, attractive int
eractions between ''spherical caps'' on the surfaces of the protein po
lyions. An equation of state is derived using perturbation theory. Fro
m this equation of state we calculate liquid-liquid equilibria: equili
brium between an aqueous phase dilute in protein and another aqueous p
hase rich in protein, which represents ''precipitated'' protein. In th
e equation of state, center-to-center, spherically symmetric macroion-
macroion interactions are described by the random-phase approximation
, while the orientation-dependent short-range hydrophobic interaction
is incorporated through the perturbation theory of associating fluids.
The results suggest that either ion-excluded-volume or hydrophobic-bo
nding effects can precipitate proteins in aqueous solutions with high
salt concentrations.