Recent Advances in the Understanding of Protein Crystallization

ABSTRACT Due to its practical significance, the crystallization of proteins is the subject of extensive research. Especially in the pharmaceutical industry, crystalline proteins must conform to specifications, such as polymorphic form, crystal number, polydispersity, shape, and crystal size distribution (CSD). However, to direct crystallization towards obtaining products with the desired specifications, a detailed understanding of protein crystallization is a must. Unfortunately, though recent years have witnessed significant progress in the general theory of crystallization, there is still much to be desired concerning the explanation of the crystallization of biomolecules: In its present state, this explanation is based solely on general physicochemical principles, while the biochemical nature of protein molecules is largely ignored. Though, to increase its predictive power, the theory of protein crystallization must also take into account proteins‘ biochemistry. To this aim, rates of nucleation of protein crystals and their further growth are reconsidered in this paper. And in doing so, a new equation describing the rate of growth of the just‐born crystals is conceived. Finally, due attention is paid to the role of water molecules in the crystallization of proteins.