title: Statistical removal of background signals from high-throughput (1)H NMR line-broadening ligand-affinity screens.
abstract: NMR ligand-affinity screens are vital to drug discovery, are routinely used to screen fragment-based libraries, and used to verify chemical leads from high-throughput assays and virtual screens. NMR ligand-affinity screens are also a highly informative first step towards identifying functional epitopes of unknown proteins, as well as elucidating the biochemical functions of protein-ligand interaction at their binding interfaces. While simple one-dimensional (1)H NMR experiments are capable of indicating binding through a change in ligand line shape, they are plagued by broad, ill-defined background signals from protein (1)H resonances. We present an uncomplicated method for subtraction of protein background in high-throughput ligand-based affinity screens, and show that its performance is maximized when phase-scatter correction is applied prior to subtraction.
authors.affiliation: Department of Chemistry, University of Nebraska-Lincoln, Lincoln, NE, 68588-0304, USA.
authors.forename: Bradley
authors.initials: B
authors.lastname: Worley
authors.affiliation: Department of Chemistry, University of Nebraska-Lincoln, Lincoln, NE, 68588-0304, USA.|Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ, 85287, USA.|Magnetic Resonance Research Center, Arizona State University, Tempe, AZ, 85287, USA.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Sisco
authors.affiliation: Department of Chemistry, University of Nebraska-Lincoln, Lincoln, NE, 68588-0304, USA. rpowers3@unl.edu.
authors.forename: Robert
authors.initials: R
authors.lastname: Powers
mesh_terms: D000465:Algorithms; D000818:Animals; D002417:Cattle; D057166:High-Throughput Screening Assays; D008024:Ligands; D019906:Nuclear Magnetic Resonance, Biomolecular; D066244:Proton Magnetic Resonance Spectroscopy; D012710:Serum Albumin, Bovine / Q000737:chemistry; D012815:Signal Processing, Computer-Assisted; D013223:Statistics as Topic
chemical_list: D008024:Ligands; D012710:Serum Albumin, Bovine
keywords: High-throughput screening; Ligand-based affinity screening; NMR; Phase-scatter correction