Protein Crystal Growth

The biological activity of most proteins is determined by their 3D structure. For instance, a substantial number of molecular diseases are caused by protein structural alterations, which are genetically encoded. Drugs operate by binding to proteins, inducing alteration of their functional structure and thereby affecting their biological activity. Hence the design and improvement of drugs is greatly facilitated by knowledge of the 3D structures of their macromolecular targets. In the light of these considerations, it is clear that elucidation of the 3D structure of proteins is of prime importance for understanding the underlying mechanisms of molecular diseases. It was initially believed that any protein that could be made soluble and could be purified would be relatively easy to crystallize. However, the results have indicated that solubility and purity of proteins, although being important factors, do not secure a yield of useful crystals. The crystallization behavior of proteins turns out to be very complex. In an effort to identify the naturally occurring protein folds, large structural genomics consortia were set up. The somewhat disappointing outcome of these efforts is that only about 3% of all proteins that were targeted by these consortia yielded a crystal structure (http://targetdb.pdb.org/statistics/TargetStatistics.html), despite massive investments in high-throughput, automated protein production, purification and crystallization. It is clear that in order to improve the current situation, better strategies for protein crystallization are required, combined with techniques that allow the use of smaller nano-crystalline material.