Protein Structure Analysis: High-throughput Approaches

Developments in the high-throughput analysis of protein structure have been primarily driven by worldwide structural genomics initiatives that are aimed at determining the three-dimensional structures of all proteins and other important biomolecules encoded by the genomes of key organisms. Structural genomics requires a large number of procedural steps in order to convert sequence information into a three-dimensional structure; this has led to new high-throughput methods for protein production, characterization, and structure determination. Over the past decade, the most notable technological advances have been in the fields of X-ray crystallography and NMR—the principal tools of structural genomics—which have facilitated high-throughput, rapid, and cost-effective structure determinations. In recent years, these developments have resulted in an exponential increase in the number of structures being deposited in the Protein Data Bank (PDB; http://www.rcsb.org/pdb/), in which the total number currently exceeds 30 000. Major developments in the fields of bioinformatics, protein production, and structure determination, and the impact of these on high-throughput protein structure analysis will be discussed in what follows.