  In this perspective we address the question: why are proteins seemingly so
hard to crystallize? We suggest that this is because of evolutionary negative
design, i.e. proteins have evolved not to crystallize, because crystallization,
as with any type of protein aggregation, compromises the viability of the cell.
There is much evidence in the literature that supports this hypothesis,
including the effect of mutations on the crystallizability of a protein, the
correlations found in the properties of crystal contacts in bioinformatics
databases, and the positive use of protein crystallization by bacteria and
viruses.
