IS THERE ANY MERIT IN COMPARING SMALL MOLECULE AND PROTEIN CRYSTALLIZATION?

Franz Rosenberger

Center for Microgravity and Materials Research, University of Alabama in Huntsville, Huntsville, AL 35899, USA, email:fros@cmmr.uah.edu

Keywords: Crystallization phenomena, interaction distance, phase separation

It is traditionally claimed that little can be learned from small molecule crystallization concepts for macromolecular crystal growth. Numerous experimental and simulation studies of the nucleation and growth kinetics of globular proteins prove this supposition wrong. In light of the common underlying physico-chemical principles, it is not surprising to find strong analogies between these two groups of solution growth systems. As a consequence, the crystallization conditions (purity, supersaturation, transport in the solution, etc.) need to be as closely controlled to obtain structurally perfect protein crystals for high-resolution structure studies as in the growth of inorganic crystals for high-performance opto-electronic device applications. There are, of course, some fundamental differences between these two material groups. These root mostly in the small ratio of the interaction distance to the molecule diameter characteristic of proteins in solutions under crystallization conditions. Such macromolecule-specific phenomena include metastable liquid-liquid phase separation and gelation, which, in laboratory lingo, are known as "oiling out", "amorphous precipitates", etc. But again, these cumbersome phenomena can be readily understood and, thus, controlled in terms of general principles underlying phase transitions. Hence, insight into small molecule crystallization principles can be very beneficial for the protein crystallization practice. In turn, inorganic systems have most recently benefited from investigations of protein crystallization kinetics that revealed nonlinear phenomena underlying the formation of structural defects in crystallization in general. Thus small molecule and protein crystallization studies are truly synergistic.