Protein crystallization

This essay is about the crystallization of proteins. Since the first published observation of crystallizing proteins about 160 years ago, protein crystal growth has developed into an extensive research field with many applications, for instance in the pharmaceutical industry. In this report, an overview of the unique physical-chemical characteristics of protein molecules, their properties in solution and their properties in the crystalline state, together with a description of some important aspects of protein crystallization and research in this field, is given. Seven proteins that are the main models of crystallization studies are presented, just as the general (thermodynamic) principles applying to protein crystal growth and the main parameters influencing the process. The most commonly used protein crystallization techniques are described, together with their underlying principles and the approaches used to find suitable conditions for crystallization of a particular protein. Focusing on the fundamental studies of protein crystallization on a molecular level, the current knowledge of nucleation processes, crystal growth mechanisms and kinetics is summarized. Concluding this essay, an inventory is made of knowledge that is still missing, but that is crucial in order to develop a more directed crystallization approach. Suggestions for future research, aimed at obtaining this insight, are given.