Advances in protein NMR provided by the NIGMS Protein Structure Initiative: impact on drug discovery.

Rational drug design relies on the 3D structures of biological macromolecules, with a particular emphasis on proteins. The structural genomics-based high-throughput structure determination platforms established by the Protein Structure Initiative (PSI) of the National Institute of General Medical Science (NIGMS) of the NIH are uniquely suited to provide these structures. NMR plays a critical role in structure determination because many important protein targets do not form the single crystals required for X-ray diffraction. NMR can provide valuable structural and dynamic information on proteins and their drug complexes that cannot be obtained with X-ray crystallography. This review discusses recent advances in NMR that have been driven by structural genomics projects. These advances suggest that the future discovery and design of drugs can increasingly rely on protocols using NMR approaches for the rapid and accurate determination of structures.