Phenomenological Consideration of Protein Crystal Nucleation; the Physics and Biochemistry behind the Phenomenon

Abstract

Physical and biochemical aspects of protein crystal nucleation can be distinguished in an appropriately designed experimental setting. From a physical perspective, the diminishing number of nucleation-active particles (and/or centers), and the appearance of nucleation exclusion zones, are two factors that act simultaneously and retard the initially fast heterogeneous nucleation, thus leading to a logistic time dependence of nuclei number density. Experimental data for protein crystal (and small-molecule droplet) nucleation are interpreted on this basis. Homogeneous nucleation considered from the same physical perspective reveals a difference—the nucleation exclusion zones lose significance as a nucleation decelerating factor when their overlapping starts. From that point on, a drop of overall system supersaturation becomes the sole decelerating factor. Despite the different scenarios of both heterogeneous and homogeneous nucleation, S-shaped time dependences of nuclei number densities are practically indistinguishable due to the exponential functions involved. The biochemically conditioned constraints imposed on the protein crystal nucleation are elucidated as well. They arise because of the highly inhomogeneous (patchy) protein molecule surface, which makes bond selection a requisite for protein crystal nucleation (and growth). Relatively simple experiments confirm this assumption.