On the Slow Kinetics of Protein Crystallization

Abstract

Although they require surprisingly high supersaturations, both nucleation and growth of protein crystals proceed substantially more slowly as compared to small molecule crystallization. The slow nucleation of the protein crystals is explained by the steric restriction for association of the protein molecules that is due to their highly inhomogeneous surfaces. Over their surfaces, the proteins exhibit a limited number of discrete patches that are the only attractive portions on the molecule. A simple model for protein crystal nucleation has been devised on this basis, which enables calculations of nucleus form, energy barrier, and probability for nucleus formation. It turns out that the unusually high supersaturations used experimentally are necessary for the formation of relatively small nuclei, because the probability for bigger fluctuations is negligibly small. On the other hand, the big size of the protein molecules contributes additionally for the slow growth of the protein crystals. It causes huge Burgers vectors of the dislocations. In turn, this leads to a locally increased chemical potential and an effective decrease of the local supersaturation at the step source.