The future of protein crystal growth

Abstract

Crystallographic studies of biological macromolecules have proved of great value in establishing the structural foundations of biochemistry and molecular biology, and for revealing structure/function relationships that are of importance in our understanding of how enzymes, nucleic acids, and other macromolecules operate in biological systems. There have been major advances in the technology involved in determining protein crystal structures, once suitable crystals are available. The major bottleneck in the widespread application of protein crystallography is the difficulty in obtaining large, high-quality crystals of biological macromolecules for structural analysis. Most macromolecules are difficult to crystallize, and many otherwise exciting and promising projects have terminated at the crystal growth stage. Even when large crystals are obtained, the crystals of essentially all biological macromolecules diffract poorly due to internal disorder in these crystals. Despite the need to better understand protein crystal growth, this field has received only limited attention in the past. Since protein crystals are stabilized by rather weak interactions, they are extremely sensitive to subtle variations in solution conditions; consequently, protein crystal growth presents particularly challenging problems. However, considering the great importance of protein crystal growth, it is likely that this field will develop rapidly during the next few years.