title: Structural biology in fragment-based drug design.
abstract: Fragment-based ligand screening is now established as an emerging paradigm for drug discovery. Here we examine the recent literature looking at how structural biology has been used in a variety of successful fragment-screening applications. We argue that the determination of experimental binding modes has proved to be one of the mainstays of successful fragment-based approaches and that this reflects the difficulty in optimising a fragment to a lead molecule in the absence of structural information. We focus on antimicrobial research where fragment-based drug discovery allows control of the physical properties of the emerging lead molecule.
authors.affiliation: Astex Therapeutics Ltd., 436 Cambridge Science Park, Milton Road, Cambridge CB4 0QA, United Kingdom.
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Murray
authors.forename: Tom L
authors.initials: TL
authors.lastname: Blundell
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology; D001695:Biology / Q000379:methods*; D018360:Crystallography, X-Ray; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006801:Humans; D009682:Magnetic Resonance Spectroscopy
chemical_list: D000890:Anti-Infective Agents