The interaction energy between two protein molecules related to physical properties of their solution and their crystals and implications for crystal growth

Abstract

Protein crystallization is an essential step, and often a bottleneck, in the structure determination of a protein by X-ray diffraction. It is the least understood step in the process of structure determination. In this article a study, based on a simple lattice model, is presented to relate the free energy of interaction of the protein molecules in the crystal with their solubility as well as with the surface energy of the crystal. The most remarkable result is that the interaction energy is fairly constant for different proteins in their crystals: − (63 ± 3) × 10 − 21 J. We conclude that the search for optimal crystallization conditions corresponds to adjusting the interaction energy between the protein molecules to this value. For the surface energy of the crystals higher values are calculated than the experimental values reported in the literature by Malkin and McPherson [J. Crystal Growth 128 (1993) 1232; 133 (1993) 29]. However, the latter are obtainedfor small nuclei which may be rather disordered assemblies of protein molecules.