Biomolecular interactions in solution include a variety of effects: hard sp
here, electrostatic, van der Waals, hydrophobic, etc. The corresponding int
eraction potentials govern the macromolecular distribution in solution, the
shapes of the phase diagrams and the crystallization process. Different te
chniques: small angle X-ray scattering (SAXS), light scattering, osmotic pr
essure, can be used to characterize these potentials. Here, SAXS was the to
ol of choice to follow the changes induced by the crystallizing agents in d
ifferent physicochemical conditions. Moreover, the coupling of SAXS (experi
mental structure factors) and numerical simulations derived from statistica
l mechanics (calculated structure factors) allowed us to determine the best
fit parameters of the relevant potentials. Several protein model systems h
ave now been investigated, with different isoelectric points, sizes and com
pactness, After the studies performed on lysozyme, and on aspartate transca
rbamylase (ATCase), we proceeded with lens gamma- and alpha-crystallins and
with urate oxidase. We can now draw the following picture of the relevant
potentials. With low molecular weight proteins, a coulombic, pH dependent,
repulsive potential and a short range (a few Angstrom), possibly van der Wa
als, attraction are sufficient to account for the behavior observed at low
ionic strength. At higher ionic strength, the salt specific effects that fo
llow the (direct or reverse) order of the Hofmeister series, correspond to
an additional short range salt specific attraction. With increasing protein
size, the van der Waals contribution becomes negligible. The addition of p
olymers like polyethylene glycol (PEG) induces a depletion mechanism, which
is equivalent to a protein-protein attraction. Crystallization definitivel
y appears to be under control of sufficiently strong and short range (a few
Angstrom) attractions, which means that, despite the diversity of protein
sequences, it is possible to define a range of physicochemical conditions t
hat may generate crystals. Yet, if salt addition appears to be sufficient t
o provide such conditions with small compact proteins, additives like PEG s
eem to be required at higher molecular weights. The success, of course, wil
l also rely upon the protein purity and stability. (C) 2001 Elsevier Scienc
e B.V. All rights reserved.