title: NMR screening in fragment-based drug design: a practical guide.
abstract: Fragment-based drug design (FBDD) comprises both fragment-based screening (FBS) to find hits and elaboration of these hits to lead compounds. Typical fragment hits have lower molecular weight (<300-350 Da) and lower initial potency but higher ligand efficiency when compared to those from high-throughput screening. NMR spectroscopy has been widely used for FBDD since it identifies and localizes the binding site of weakly interacting hits on the target protein. Here we describe ligand-based NMR methods for hit identification from fragment libraries and for functional cross-validation of primary hits.
authors.affiliation: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ, 07033, USA, hai-young.kim@merck.com.
authors.forename: Hai-Young
authors.initials: HY
authors.lastname: Kim
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Wyss
mesh_terms: D001667:Binding, Competitive; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods* / Q000592:standards; D017408:Guidelines as Topic; D057166:High-Throughput Screening Assays / Q000379:methods / Q000592:standards; D008024:Ligands; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D011485:Protein Binding; D011786:Quality Control
chemical_list: D008024:Ligands