Fragment-based screening by ligand-observed 1D NMR and binding interface mapping by protein-observed 2D NMR are popular methods used in drug discovery. These methods allow researchers to detect compound binding over a wide range of affinities and offer a simultaneous assessment of solubility, purity, and chemical formula accuracy of the target compounds and the ^(15)N-labeled protein when examined by 1D and 2D NMR, respectively. These methods can be applied for screening fragment binding to the...
[NMR paper] Ligand 1 H NMR Chemical Shifts as Accurate Reporters for Protein-Ligand Binding Interfaces in Solution
Ligand 1 H NMR Chemical Shifts as Accurate Reporters for Protein-Ligand Binding Interfaces in Solution
The availability of high-resolution 3D structural information is crucial for investigating guest-host systems across a wide range of fields. In the context of drug discovery, the information is routinely used to establish and validate structure-activity relationships, grow initial hits from screening campaigns, and to guide molecular docking. For the generation of protein-ligand complex structural information, X-ray crystallography is the experimental method of choice, however, with...
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11-13-2023 06:35 PM
[NMR paper] Determination of Ligand-Binding Affinity (Kd) Using Transverse Relaxation Rate (R2) in the Ligand-Observed 1H NMR Experiment and Applications to Fragment-Based Drug Discovery
Determination of Ligand-Binding Affinity (Kd) Using Transverse Relaxation Rate (R2) in the Ligand-Observed 1H NMR Experiment and Applications to Fragment-Based Drug Discovery
High hit rates from initial ligand-observed NMR screening can make it challenging to prioritize which hits to follow up, especially in cases where there are no available crystal structures of these hits bound to the target proteins or other strategies to provide affinity ranking. Here, we report a reproducible, accurate, and versatile quantitative ligand-observed NMR assay, which can determine K(d) values of fragments...
[NMR paper] Determination of intracellular protein-ligand binding affinity by competition binding in-cell NMR
Determination of intracellular protein-ligand binding affinity by competition binding in-cell NMR
Structure-based drug development suffers from high attrition rates due to the poor activity of lead compounds in cellular and animal models caused by low cell penetrance, off-target binding or changes in the conformation of the target protein in the cellular environment. The latter two effects cause a change in the apparent binding affinity of the compound, which is indirectly assessed by cellular activity assays. To date, direct measurement of the intracellular binding affinity remains a...
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[NMR paper] Solution NMR Studies of the Ligand-Binding Domain of an Orphan Nuclear Receptor Reveals a Dynamic Helix in the Ligand-Binding Pocket.
Solution NMR Studies of the Ligand-Binding Domain of an Orphan Nuclear Receptor Reveals a Dynamic Helix in the Ligand-Binding Pocket.
Solution NMR Studies of the Ligand-Binding Domain of an Orphan Nuclear Receptor Reveals a Dynamic Helix in the Ligand-Binding Pocket.
Biochemistry. 2018 Mar 16;:
Authors: Daffern N, Chen Z, Zhang Y, Pick L, Radhakrishnan I
Abstract
The ligand-binding domains (LBD) of the NR5A subfamily of nuclear receptors activate transcription via ligand-dependent and ligand-independent mechanisms. The...
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03-17-2018 12:12 PM
Determination of ligand binding modes in weak proteinâ??ligand complexes using sparse NMR data
Determination of ligand binding modes in weak proteinâ??ligand complexes using sparse NMR data
Abstract
We describe a general approach to determine the binding pose of small molecules in weakly bound proteinâ??ligand complexes by deriving distance constraints between the ligand and methyl groups from all methyl-containing residues of the protein. We demonstrate that using a single sample, which can be prepared without the use of expensive precursors, it is possible to generate high-resolution data rapidly and obtain the resonance assignments of...
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11-19-2016 08:35 PM
[NMR paper] An investigation of the ligand-binding site of the glutamine-binding protein of Esche
An investigation of the ligand-binding site of the glutamine-binding protein of Escherichia coli using rotational-echo double-resonance NMR.
Related Articles An investigation of the ligand-binding site of the glutamine-binding protein of Escherichia coli using rotational-echo double-resonance NMR.
Biochemistry. 1994 Jul 26;33(29):8651-61
Authors: Hing AW, Tjandra N, Cottam PF, Schaefer J, Ho C
Glutamine-binding protein (GlnBP) is an essential component of the glutamine transport system in Escherichia coli. Rotational-echo double-resonance...
1D and 2D NMR for KRAS:Ligand Binding
Linear Mode
