High-throughput crystallization and structure determination in drug discovery

High-throughput protein X-ray crystallography offers an unprecedented opportunity to facilitate drug discovery. The key bottlenecks in the path from target gene to three-dimensional protein structure determination are defined. Special emphasis is placed on the concept that drug discovery projects are typically directed at a key protein target whose structure must be solved within a reasonable time frame to have an impact on the drug discovery process. The time-sensitive nature of structural data has placed growing pressure on the need to automate all aspects of protein crystallography, from gene identification to model building and refinement. Current technological innovations and strategies for automation are discussed with respect to the bottleneck they are intended to eliminate.