title: Screening Ligands by X-ray crystallography.
abstract: X-ray crystallography is an invaluable technique in structure-based drug discovery, including fragment-based drug discovery, because it is the only technique that can provide a complete three dimensional readout of the interaction between the small molecule and its macromolecular target. X-ray diffraction (XRD) techniques can be employed as the sole method for conducting a screen of a fragment library, or it can be employed as the final technique in a screening campaign to confirm putative "hit" compounds identified by a variety of biochemical and/or biophysical screening techniques. Both approaches require an efficient technique to prepare dozens to hundreds of crystals for data collection, and a reproducible way to deliver ligands to the crystal. Here, a general method for screening cocktails of fragments is described. In cases where X-ray crystallography is employed as a method to verify putative hits, the cocktails of fragments described below would simply be replaced with single fragment solutions.
authors.affiliation: Emerald Bio, 7869 NE Day Road W, Bainbridge Island, WA, 98110, USA, ddavies@embios.com.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Davies
mesh_terms: D001665:Binding Sites; D001703:Biophysics; D018360:Crystallography, X-Ray; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008967:Molecular Biology / Q000379:methods*; D054852:Small Molecule Libraries / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: D008024:Ligands; D054852:Small Molecule Libraries