Related ArticlesDetermination of protein-ligand binding modes using fast multi-dimensional NMR with hyperpolarization.
Chem Sci. 2020 Jun 21;11(23):5935-5943
Authors: Wang Y, Kim J, Hilty C
Abstract
Elucidation of small molecule-protein interactions provides essential information for understanding biological processes such as cellular signaling, as well as for rational drug development. Here, multi-dimensional NMR with sensitivity enhancement by dissolution dynamic nuclear polarization (D-DNP) is shown to allow the determination of the binding epitope of folic acid when complexed with the target dihydrofolate reductase. Protein signals are selectively enhanced by polarization transfer from the hyperpolarized ligand. A pseudo three-dimensional data acquisition with ligand-side Hadamard encoding results in protein-side [13C, 1H] chemical shift correlations that contain intermolecular nuclear Overhauser effect (NOE) information. A scoring function based on this data is used to select pre-docked ligand poses. The top five poses are within 0.76 Å root-mean-square deviation from a reference structure for the encoded five protons, showing improvements compared with the poses selected by an energy-based scoring function without experimental inputs. The sensitivity enhancement provided by the D-DNP combined with multi-dimensional NMR increases the speed and potentially the selectivity of structure elucidation of ligand binding epitopes.
High field hyperpolarization-EXSY experiment for fast determination of dissociation rates in SABRE complexes
From The DNP-NMR Blog:
High field hyperpolarization-EXSY experiment for fast determination of dissociation rates in SABRE complexes
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Hermkens, N.K.J., et al., High field hyperpolarization-EXSY experiment for fast determination of dissociation rates in SABRE complexes. J. Magn. Reson., 2017. 276: p. 122-127.
https://doi.org/10.1016/j.jmr.2017.01.011
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05-24-2017 07:40 PM
[NMR paper] Probing the Binding Modes of a Multi-Domain Protein to Lipid-Based Nanoparticles by Relaxation-Based NMR.
Probing the Binding Modes of a Multi-Domain Protein to Lipid-Based Nanoparticles by Relaxation-Based NMR.
Related Articles Probing the Binding Modes of a Multi-Domain Protein to Lipid-Based Nanoparticles by Relaxation-Based NMR.
J Phys Chem Lett. 2017 May 22;:
Authors: Ceccon A, Tugarinov V, Boughton AJ, Fushman D, Clore GM
Abstract
The interactions of two model multi-domain proteins - covalently linked di-ubiquitins, Ub2 - with lipid-based nanoparticles have been quantitatively probed by the measurements of NMR lifetime...
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05-23-2017 04:45 PM
NMR line shape analysis of a multi-state ligand binding mechanism in chitosanase
NMR line shape analysis of a multi-state ligand binding mechanism in chitosanase
Abstract
Chitosan interaction with chitosanase was examined through analysis of spectral line shapes in the NMR HSQC titration experiments. We established that the substrate, chitosan hexamer, binds to the enzyme through the three-state induced-fit mechanism with fast formation of the encounter complex followed by slow isomerization of the bound-state into the final conformation. Mapping of the chemical shift perturbations in two sequential steps of the mechanism...
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04-10-2017 12:51 AM
[NMR paper] Fast NMR-Based Determination of the 3D Structure of the Binding Site of Protein-Ligand Complexes with Weak Affinity Binders.
Fast NMR-Based Determination of the 3D Structure of the Binding Site of Protein-Ligand Complexes with Weak Affinity Binders.
Fast NMR-Based Determination of the 3D Structure of the Binding Site of Protein-Ligand Complexes with Weak Affinity Binders.
Angew Chem Int Ed Engl. 2017 Apr 07;:
Authors: Wälti MA, Riek R, Orts J
Abstract
In early drug discovery approaches, screening hits are often weak affinity binders that are difficult to characterize in structural detail, particularly towards obtaining the 3D structure of...
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04-08-2017 10:57 AM
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] Fast multi-dimensional NMR acquisition and processing using the sparse FFT.
Fast multi-dimensional NMR acquisition and processing using the sparse FFT.
http://www.bionmr.com//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--production.springer.de-OnlineResources-Logos-springerlink.gif Related Articles Fast multi-dimensional NMR acquisition and processing using the sparse FFT.
J Biomol NMR. 2015 Sep;63(1):9-19
Authors: Hassanieh H, Mayzel M, Shi L, Katabi D, Orekhov VY
Abstract
Increasing the dimensionality of NMR experiments strongly enhances the spectral resolution and provides invaluable direct...
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06-21-2016 01:30 PM
Fast multi-dimensional NMR acquisition and processing using the sparse FFT
Fast multi-dimensional NMR acquisition and processing using the sparse FFT
Abstract
Increasing the dimensionality of NMR experiments strongly enhances the spectral resolution and provides invaluable direct information about atomic interactions. However, the price tag is high: long measurement times and heavy requirements on the computation power and data storage. We introduce sparse fast Fourier transform as a new method of NMR signal collection and processing, which is capable of reconstructing high quality spectra of large size and dimensionality...
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06-30-2015 11:41 AM
[NMR paper] Fast multi-dimensional NMR of proteins.
Fast multi-dimensional NMR of proteins.
Related Articles Fast multi-dimensional NMR of proteins.
J Biomol NMR. 2003 Apr;25(4):349-54
Authors: Kupce E, Freeman R
Three-dimensional HNCO and HNCA subspectra from a small protein (agitoxin, 4 kDa, enriched in carbon-13 and nitrogen-15), have been obtained by direct frequency-domain excitation of selected carbon and nitrogen sites. This new technique applies an array of several simultaneous soft radiofrequency spin-inversion pulses, encoded (on or off) according to nested Hadamard matrices, and the...
Determination of protein-ligand binding modes using fast multi-dimensional NMR with hyperpolarization.
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