Structures of Trypanosoma brucei Methionyl-tRNA Synthetase with Urea-Based Inhibitors Provide Guidance for Drug Design against Sleeping Sickness

10.1371/journal.pntd.0002775PLoS Neglected Tropical Diseases84e277

DRUG OR TOOL, DESIGN OR SERENDIPITY

Iterative protein structure-based ligand design has led to a 'selective' inhibitor of human non-pancreatic secretory phospholipase A2 which provides a new tool for probing metabolic pathways and may lead to a useful drug.

Structural biology and bioinformatics in drug design: opportunities and challenges for target identification and lead discovery

Impressive progress in genome sequencing, protein expression and high-throughput crystallography and NMR has radically transformed the opportunities to use protein three-dimensional structures to accelerate drug discovery, but the quantity and complexity of the data have ensured a central place for informatics. Structural biology and bioinformatics have assisted in lead optimization and target identification where they have well established roles; they can now contribute to lead discovery, exploiting high-throughput methods of structure determination that provide powerful approaches to screening of fragment binding