Related ArticlesNMRmix: A Tool for the Optimization of Compound Mixtures in 1D (1)H NMR Ligand Affinity Screens.
J Proteome Res. 2016 Mar 11;
Authors: Stark JL, Eghbalnia HR, Lee W, Westler WM, Markley JL
Abstract
NMR ligand affinity screening is a powerful technique that is routinely used in drug discovery or functional genomics to directly detect protein-ligand binding events. Binding events can be identified by monitoring differences in the one-dimensional (1)H NMR spectrum of a compound with and without protein. Although a single NMR spectrum can be collected within a short period (2-10 min per sample), one-by-one screening of a protein against a library of hundreds or thousands of compounds requires a large amount of spectrometer time and a large quantity of protein. To improve the efficiency of these screens in both time and material, compounds are usually evaluated in mixtures ranging in size from 3 to 20 compounds. Ideally, the NMR signals from individual compounds in the mixture should not overlap so that spectral changes can be associated with a particular compound. We have developed a software tool, NMRmix, to assist in creating ideal mixtures from a large panel of compounds with known chemical shifts. Input to NMRmix consists of a (1)H NMR peak list for each compound, a user-defined overlap threshold, and additional user-defined parameters if default settings are not used. NMRmix utilizes a simulated annealing algorithm to optimize the composition of the mixtures to minimize spectral peak overlaps so that each compound in the mixture is represented by a maximum number of non-overlapping chemical shifts. A built-in graphical user interface simplifies data import and visual evaluation of the results.
PMID: 26965640 [PubMed - as supplied by publisher]
[NMR paper] Statistical removal of background signals from high-throughput (1)H NMR line-broadening ligand-affinity screens.
Statistical removal of background signals from high-throughput (1)H NMR line-broadening ligand-affinity screens.
Statistical removal of background signals from high-throughput (1)H NMR line-broadening ligand-affinity screens.
J Biomol NMR. 2015 Jul 9;
Authors: Worley B, Sisco NJ, Powers R
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...
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07-12-2015 07:12 AM
Statistical removal of background signals from high-throughput 1 H NMR line-broadening ligand-affinity screens
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 proteinā??ligand interaction at their binding interfaces....
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07-08-2015 11:11 PM
Protein-ligand docking guided by ligand pharmacophore-mapping experiment by NMR.
Protein-ligand docking guided by ligand pharmacophore-mapping experiment by NMR.
Protein-ligand docking guided by ligand pharmacophore-mapping experiment by NMR.
J Mol Graph Model. 2011 Sep 3;
Authors: Fukunishi Y, Mizukoshi Y, Takeuchi K, Shimada I, Takahashi H, Nakamura H
Abstract
We developed a new protein-ligand docking calculation method using experimental NMR data. Recently, we proposed a novel ligand epitope-mapping experiment, which utilizes the difference between the longitudinal relaxation rates of ligand protons with and...
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09-24-2011 04:11 PM
Ultrafast quantitative 2D NMR: an efficient tool for the measurement of specific isotopic enrichments in complex biological mixtures.
Ultrafast quantitative 2D NMR: an efficient tool for the measurement of specific isotopic enrichments in complex biological mixtures.
Ultrafast quantitative 2D NMR: an efficient tool for the measurement of specific isotopic enrichments in complex biological mixtures.
Anal Chem. 2011 Apr 15;83(8):3112-9
Authors: Giraudeau P, Massou S, Robin Y, Cahoreau E, Portais JC, Akoka S
Two-dimensional nuclear magnetic resonance (2D NMR) is a promising tool for studying metabolic fluxes by measuring (13)C-enrichments in complex mixtures of (13)C-labeled...
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08-04-2011 11:41 AM
[NMR paper] Determination of protein-ligand binding affinity by NMR: observations from serum albu
Determination of protein-ligand binding affinity by NMR: observations from serum albumin model systems.
Related Articles Determination of protein-ligand binding affinity by NMR: observations from serum albumin model systems.
Magn Reson Chem. 2005 Jun;43(6):463-70
Authors: Fielding L, Rutherford S, Fletcher D
The usefulness of bovine serum albumin (BSA) as a model protein for testing NMR methods for the study of protein-ligand interactions is discussed. Isothermal titration calorimetry established the binding affinity and stoichiometry of the...
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11-25-2010 08:21 PM
[NMR paper] Chemical proteomic tool for ligand mapping of CYP antitargets: an NMR-compatible 3D Q
Chemical proteomic tool for ligand mapping of CYP antitargets: an NMR-compatible 3D QSAR descriptor in the Heme-Based Coordinate System.
Related Articles Chemical proteomic tool for ligand mapping of CYP antitargets: an NMR-compatible 3D QSAR descriptor in the Heme-Based Coordinate System.
J Chem Inf Comput Sci. 2004 Jul-Aug;44(4):1456-65
Authors: Yao H, Costache AD, Sem DS
Chemical proteomic strategies strive to probe and understand protein-ligand interactions across gene families. One gene family of particular interest in drug and xenobiotic...
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11-24-2010 09:51 PM
[NMR paper] Spin labels as a tool to identify and characterize protein-ligand interactions by NMR
Spin labels as a tool to identify and characterize protein-ligand interactions by NMR spectroscopy.
Related Articles Spin labels as a tool to identify and characterize protein-ligand interactions by NMR spectroscopy.
Chembiochem. 2002 Mar 1;3(2-3):167-73
Authors: Jahnke W
NMR spectroscopy based discovery and optimization of lead compounds for a given molecular target requires the development of methods with maximum sensitivity and robustness. It is shown here that organic nitroxide radicals ("spin labels") can be used to boost the sensitivity...
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11-24-2010 08:49 PM
[NMR paper] On the ligand-protein and ligand-flavin interactions in NADPH-adrenodoxin reductase a
On the ligand-protein and ligand-flavin interactions in NADPH-adrenodoxin reductase as studied by 31P- and 13C-NMR. Use of 13C-enriched FAD as a probe.
Related Articles On the ligand-protein and ligand-flavin interactions in NADPH-adrenodoxin reductase as studied by 31P- and 13C-NMR. Use of 13C-enriched FAD as a probe.
J Biochem. 1991 Jan;109(1):144-9
Authors: Fujii S, Nonaka Y, Okamoto M, Miura R
The interaction between 2',5'-ADP and NADPH-adrenodoxin reductase from bovine adrenocortical mitochondria was examined by titrating the enzyme with...
NMRmix: A Tool for the Optimization of Compound Mixtures in 1D (1)H NMR Ligand Affinity Screens.
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