High-throughput crystallography for lead discovery: successes and challenges
نویسنده
چکیده
Knowledge of the three-dimensional structures of protein targets now emerging from genomic data has the potential to accelerate greatly drug discovery, but technical challenges and time constraints have traditionally limited their use primarily to lead optimization. Their application is now being extended beyond structure determination, into new approaches for lead discovery (for review see Blundell et al.,2002). Virtual screening coupled with high throughput X-ray crystallography is focused on identifying one or more weakly binding small-molecule fragments from compound libraries consisting of hundreds of smallmolecule fragments. The high-resolution definition of this binding interaction provides an information-rich starting point for medicinal chemistry. The use of high throughput X-ray crystallography does not end there, as it becomes a rapid technique to guide the elaboration of the fragments into larger molecular weight lead compounds.
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