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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.

SUBMITTER: Worley B

PROVIDER: S-EPMC4577452 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Statistical removal of background signals from high-throughput (1)H NMR line-broadening ligand-affinity screens.

Worley Bradley B Sisco Nicholas J NJ Powers Robert R

Journal of biomolecular NMR 20150709 1

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 in ...[more]

PMID: 26156049

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