Mass spectrometric characterization of a protein-ligand interaction

1995 ◽  
Vol 117 (4) ◽  
pp. 1374-1377 ◽  
Author(s):  
Robert J. Anderegg ◽  
David S. Wagner
Biomolecules ◽  
2018 ◽  
Vol 8 (3) ◽  
pp. 61 ◽  
Author(s):  
Fernando Prieto-Martínez ◽  
José Medina-Franco

Flavonoids are widely recognized as natural polydrugs, given their anti-inflammatory, antioxidant, sedative, and antineoplastic activities. Recently, different studies showed that flavonoids have the potential to inhibit bromodomain and extraterminal (BET) bromodomains. Previous reports suggested that flavonoids bind between the Z and A loops of the bromodomain (ZA channel) due to their orientation and interactions with P86, V87, L92, L94, and N140. Herein, a comprehensive characterization of the binding modes of fisetin and the biflavonoid, amentoflavone, is discussed. To this end, both compounds were docked with BET bromodomain 4 (BRD4) using four docking programs. The results were post-processed with protein–ligand interaction fingerprints. To gain further insight into the binding mode of the two natural products, the docking results were further analyzed with molecular dynamics simulations. The results showed that amentoflavone makes numerous contacts in the ZA channel, as previously described for flavonoids and kinase inhibitors. It was also found that amentoflavone can potentially make contacts with non-canonical residues for BET inhibition. Most of these contacts were not observed with fisetin. Based on these results, amentoflavone was experimentally tested for BRD4 inhibition, showing activity in the micromolar range. This work may serve as the basis for scaffold optimization and the further characterization of flavonoids as BET inhibitors.


Author(s):  
Fernando Daniel Prieto-Martínez ◽  
José Luis Medina-Franco

Flavonoids are widely recognized as natural polydrugs, given their anti-inflammatory, antioxidant, sedative and antineoplastic activities. Recently, different studies have shown that flavonoid have the potential to inhibit BET bromodomains. Previous reports suggest that flavonoids are putative inhibitors of the ZA channel due to their orientation and interactions with P86, V87, L92, L94 and N140. Herein, a comprehensive characterization of the binding mode of the biflavonoid amentoflavone and fisetin is discussed. To this end, both compounds were docked with BRD4 using four docking programs. Results were post-processed with protein-ligand interaction fingerprints. To gain further insights into the binding mode of the two natural products, docking results were further analyzed with molecular dynamics. Results showed that amentoflavone makes numerous contacts in the ZA channel, as previously described for flavonoids and kinase inhibitors. It was also found that amentoflavone can potentially make contacts with non-canonical residues for BET inhibition. Most of these contacts were not observed with fisetin. Based on these results, amentoflavone was tested for BRD4 inhibition, showing activity in the micromolar range. This work may serve as basis for scaffold optimization and further characterization of flavonoids as BET inhibitors.


1991 ◽  
Author(s):  
K. Balasaunmugam ◽  
K. G. Owens ◽  
K. F. Hsueh ◽  
P. Hoontrakul ◽  
M. A. Olsen

Author(s):  
Xiaodong Pang ◽  
Linxiang Zhou ◽  
Lily Zhang ◽  
Lina Xu ◽  
Xinyi Zhang

Energies ◽  
2021 ◽  
Vol 14 (8) ◽  
pp. 2123
Author(s):  
Makuachukwu F. Mbaegbu ◽  
Puspa L. Adhikari ◽  
Ipsita Gupta ◽  
Mathew Rowe

Determining gas compositions from live well fluids on a drilling rig is critical for real time formation evaluation. Development and utilization of a reliable mass spectrometric method to accurately characterize these live well fluids are always challenging due to lack of a robust and effectively selective instrument and procedure. The methods currently utilized need better calibration for the characterization of light hydrocarbons (C1–C6) at lower concentrations. The primary goal of this research is to develop and optimize a powerful and reliable analytical method to characterize live well fluid using a quadruple mass spectrometer (MS). The mass spectrometers currently being used in the field have issues with detection, spectra deconvolution, and quantification of analytes at lower concentrations (10–500 ppm), particularly for the lighter (<30 m/z) hydrocarbons. The objectives of the present study are thus to identify the detection issues, develop and optimize a better method, calibrate and QA/QC the MS, and validate the MS method in lab settings. In this study, we used two mass spectrometers to develop a selective and precise method to quantitatively analyze low level lighter analytes (C1–C6 hydrocarbons) with masses <75 m/z at concentrations 10–500 ppm. Our results suggest that proper mass selection like using base peaks with m/z 15, 26, 41, 43, 73, and 87, respectively, for methane, ethane, propane, butane, pentane, and hexane can help detect and accurately quantify hydrocarbons from gas streams. This optimized method in quadrupole mass spectrometer (QMS) will be invaluable for early characterization of the fluid components from a live hydrocarbon well in the field in real time.


Author(s):  
Lennart Gundelach ◽  
Christofer S Tautermann ◽  
Thomas Fox ◽  
Chris-Kriton Skylaris

The accurate prediction of protein-ligand binding free energies with tractable computational methods has the potential to revolutionize drug discovery. Modeling the protein-ligand interaction at a quantum mechanical level, instead of...


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