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

A robust correlation between experimentally determinable parameter, B-2/B-2 (HS), and protein solubility is explored. Here B-2 is the protein solution second virial coefficient and B-2(HS) = 2 pi sigma(3)/3 is the hard sphere second virial coefficient of the protein whose core is described as a spher e with diameter sigma. The origin of this correlation, which extends over t hree decades in solubility, is discussed in terms of the phase behavior of simple fluids composed of particles experiencing short range attractions. F or a given solubility B-2/B-2(HS) values cluster in a narrow range for a va riety of protein solution conditions. However, the value of B-2/B-2(HS) at the metastable fluid/fluid transition remains as sensitive solution conditi ons. We discuss this sensitivity in terms of phase behavior predicted for p articles interacting with the three parameter, square well and Yukawa poten tials where metastable critical points are sensitive to the range of attrac tion. The position of this critical point relative to the solubility bounda ry and the ease of crystal nucleation are found to depend on solution condi tions. (C) 1999 American Institute of Physics. [S0021-9606(99)50644-2].