High-throughput crystallography to enhance drug discovery.
Protein crystallography has traditionally been regarded as a resource-intensive, time-consuming technique that, with some notable exceptions, has not made a significant impact on drug discovery. However, inspired by successes in the genome-sequencing initiatives, recent years have seen major changes in X-ray crystallography methodologies and the concept of high-throughput crystallography has emerged. Advances have been made in all phases of the process, including improved molecular biology, protein expression, crystallization and structure determination. This transformation has allowed X-ray crystallography to impact more broadly in the drug-discovery process, extending its utility from structure-based lead optimisation to novel fragment-based lead generation approaches.
Sharff
Andrew
A
Astex Technology Ltd, 436 Cambridge Science Park, Milton Road, Cambridge, CB4 0QA, UK. a.sharff@astex-technology.com
Jhoti
Harren
H
D000818:Animals; D018360:Crystallography, X-Ray / Q000379:methods*; D006801:Humans; D010600:Pharmacology / Q000379:methods*; D013329:Structure-Activity Relationship