Proteins in solution: from X-ray scattering intensities to interaction potentials

Biological macromolecules in solution interact with each other through medi um-range (from a few Angstrom to a few nm) interaction potentials. These po tentials control the macromolecular distribution in solution, the macromole cular phase diagram and the crystallization process. We have previously sho wn that small angle X-ray scattering (SAXS) is a convenient tool to charact erize the resulting potential, either attractive or repulsive, and to follo w the changes induced by the crystallizing agents. In the present paper SAX S and simulation methods derived from statistical mechanics are coupled to determine the best fit potentials from the comparison of experimental and t heoretical intensity curves. The currently used models in the colloid field are derived from the DLVO (Derjaguin, Landau, Verwey, Overbeek) potential where three types of interactions play a major role: hard sphere and electr ostatic are repulsive, van der Waals are attractive. A combination of a sho rt-range attractive potential and a coulombic repulsive indeed correctly ac counts at low ionic strength for the phase diagram as a function of pH and salt concentration. The origin of the ion specificities at high ionic stren gth associated with the so-called "Hofmeister series" remain, however, uncl ear. The whole of the data demonstrates that the colloidal approach may be applied with success to protein crystallization. (C) 1999 Elsevier Science B.V. All rights reserved.