At low concentrations of salt, solubility of the proteins usually increases slightly (salting in). But at high concentrations of salt, the solubility of the proteins drop sharply (salting out).
Initial salting in at low concentrations is explained by the Debye-Huckel theory. Proteins are surrounded by the salt counter ions (ions of opposite net charge) and this screening results in decreasing electrostatic free energy of the protein and increasing activity of the solvent, which in turn, leads to increasing solubility. This theory predicts the logarithm of solubility to be proportional to the square root of the ionic strength.
The behavior of proteins in solutions at high salt concentrations was explained by Kirkwood. The abundance of the salt ions decreases the solvating power of the salt ions decreases the solubility of the proteins decreases and precipitation results.
At high salt concentrations, the solubility is given by the following empirical expression due to Cohn.
log S = B - KI
where S is the solubility of the protein, B is a constant (function of protein, pH and temperature) K is the salting out constant (function of pH, mixing and salt), and I is the ionic strength of the salt. Here you could plot the log of protein solubility versus the salt concentration, and it would look like this:
The slope of the salting out curve is a function of the protein and salt involved, but it is not a function of the pH and temperature. Also, as the molecular weight of the protein increases, the amount of salt required for precipitation decreases.
There is a series of the relative effectiveness of different anions in the salts used for protein precipitation. This is referred to as the lyotropic of Hofmeister series. The order is citrate > phosphate > sulphate > acetate which is about as good as chloride > nitrate > thiocyanate. There is also a similar series for cations.
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