van der Waals phase transition in protein solutions.

The van der Waals equation of state for imperfect gases is applied to solutions of macromolecules, especially to explain the fluid-fluid phase transition in protein solutions, a phenomenon of much interest in relation to protein crystallization. The van der Waals b parameter corresponds to the total excluded volume per pair of molecules and can be calculated from independently known molecular properties. It is comprised of terms resulting from hard-sphere and net charge-charge interactions. The experimentally determined second virial coefficient B2 can then be used to obtain the equilibrium constant for dimerization K2, a phenomenologically accessible measure of the van der Waals a parameter. Sedimentation equilibrium is recommended as the technique for measuring B2 most accurately. More general results are used to make a minor quantitative correction to the van der Waals prediction concerning the criterion for the fluid-fluid phase transition. Calculations of the effect of inert co-solutes on the phase transition may prove useful in choosing crystallization conditions.