Protein interactions and phase behavior: Sensitivity to the form of the pair potential

A robust correlation between experimentally determinable parameter, B2/B2HS, and protein solubility is explored. Here B2 is the protein solution second virial coefficient and B2HS=2πσ3/3 is the hard sphere second virial coefficient of the protein whose core is described as a sphere with diameter σ. The origin of this correlation, which extends over three decades in solubility, is discussed in terms of the phase behavior of simple fluids composed of particles experiencing short range attractions. For a given solubility B2/B2HS values cluster in a narrow range for a variety of protein solution conditions. However, the value of B2/B2HS at the metastable fluid/fluid transition remains as sensitive solution conditions. We discuss this sensitivity in terms of phase behavior predicted for particles interacting with the three parameter, square well and Yukawa potentials where metastable critical points are sensitive to the range of attraction. The position of this critical point relative to the solubility boundary and the ease of crystal nucleation are found to depend on solution conditions.