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.