Based on UPLC-Q-TOF-MS/MS, Systematic Network Pharmacology, and Molecular Docking to Explore the Potential Mechanism of Fructus Aurantii for Major Depression Disorder

Xie, Ya-Ting; Liu, Ying; Zheng, Peng; Zhang, Tao; Ye, Xianwen; Liu, Minmin; Huang, Min; Wan, Quan; Zhang, Jinlian

doi:10.1155/2021/6486287

Cited by 9 publications

(2 citation statements)

References 25 publications

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“…The 3D structures of BRD4-MS436 (PDB code: 4NUD) [ 42 ] and BRD4-ZL0590 (PDB code: 6u0d) [ 18 ] were obtained from the protein database ( , accessed on 2 August 2022). The water and ligand in the protein were removed by Discovery Studio [ 45 ], and Free empty protein Free-BRD4 was obtained.…”

Section: Methodsmentioning

confidence: 99%

Molecular Dynamics Simulations Combined with Markov Model to Explore the Effect of Allosteric Inhibitor Binding on Bromodomain-Containing Protein 4

Yang

Gao

Cao

et al. 2023

IJMS

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Bromodomain-Containing Protein 4 (BRD4) can play an important role in gene transcriptional regulation of tumor development and survival by participating in histone modification epigenetic mechanism. Although it has been reported that novel allosteric inhibitors such as ZL0590 have a high affinity with target protein BRD4 and good efficacy, their inhibitory mechanism has not been studied further. The aim of this study was to reveal the inhibition mechanism of allosteric inhibitor ZL0590 on Free-BRD4 and BRD4 binding MS436 (orthosteric inhibitor) by molecular dynamics simulation combined with a Markov model. Our results showed that BRD4-ZL0590 led to α-helices formation of 100–105 compared with Free-BRD4; the combination of MS436 caused residues 30–40 and 95–105 to form α-helices, while the combination of allosteric inhibitors untangled the α-helices formed by the MS436. The results of Markov flux analysis showed that the binding process of inhibitors mainly involved changes in the degree of α-helices at ZA loop. The binding of ZL0590 reduced the distance between ZA loop and BC loop, blocked the conformation at the active site, and inhibited the binding of MS436. After the allosteric inhibitor binding, the MS436 that could normally penetrate into the interior of the pocket was floating on the edge of the active pocket and did not continue to penetrate into the active pocket as expected. In summary, we provide a theoretical basis for the inhibition mechanism of ZL0590 against BRD4, which can be used as a reference for improving the development of drug targets for cancer therapy.

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Section: Methodsmentioning

confidence: 99%

Molecular Dynamics Simulations Combined with Markov Model to Explore the Effect of Allosteric Inhibitor Binding on Bromodomain-Containing Protein 4

Yang

Gao

Cao

et al. 2023

IJMS

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“…In addition, LibDock [67] was used for batch docking between the ten flavonoid molecules and NOS2. Using Discovery Studio [68] for complex fingerprint analysis, hydrogen bonding and coordination interactions between the receptor protein's active-site residues and flavonoid small molecule postures were identified. Finally, Pymol software (version 2.3.4) [69] was used to display the details of interactions between flavonoid small molecule targets.…”

Section: Compound Fingerprint Analysismentioning

confidence: 99%

Network Pharmacology Combined with Machine Learning to Reveal the Action Mechanism of Licochalcone Intervention in Liver Cancer

Guo,

Yang,

et al. 2023

IJMS

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There are reports indicating that licochalcones can inhibit the proliferation, migration, and invasion of cancer cells by promoting the expression of autophagy-related proteins, inhibiting the expression of cell cycle proteins and angiogenic factors, and regulating autophagy and apoptosis. This study aims to reveal the potential mechanisms of licochalcone A (LCA), licochalcone B (LCB), licochalcone C (LCC), licochalcone D (LCD), licochalcone E (LCE), licochalcone F (LCF), and licochalcone G (LCG) inhibition in liver cancer through computer-aided screening strategies. By using machine learning clustering analysis to search for other structurally similar components in licorice, quantitative calculations were conducted to collect the structural commonalities of these components related to liver cancer and to identify key residues involved in the interactions between small molecules and key target proteins. Our research results show that the seven licochalcones molecules interfere with the cancer signaling pathway via the NF-κB signaling pathway, PDL1 expression and PD1 checkpoint pathway in cancer, and others. Glypallichalcone, Echinatin, and 3,4,3′,4′-Tetrahydroxy-2-methoxychalcone in licorice also have similar structures to the seven licochalcones, which may indicate their similar effects. We also identified the key residues (including ASN364, GLY365, TRP366, and TYR485) involved in the interactions between ten flavonoids and the key target protein (nitric oxide synthase 2). In summary, we provide valuable insights into the molecular mechanisms of the anticancer effects of licorice flavonoids, providing new ideas for the design of small molecules for liver cancer drugs.

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Ethnopharmacology, chemical composition and functions of Citrus aurantium L

Ren,

Wang,

Zhang

et al. 2024

Food Measure

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Based on UPLC-Q-TOF-MS/MS, Systematic Network Pharmacology, and Molecular Docking to Explore the Potential Mechanism of Fructus Aurantii for Major Depression Disorder

Cited by 9 publications

References 25 publications

Molecular Dynamics Simulations Combined with Markov Model to Explore the Effect of Allosteric Inhibitor Binding on Bromodomain-Containing Protein 4

Molecular Dynamics Simulations Combined with Markov Model to Explore the Effect of Allosteric Inhibitor Binding on Bromodomain-Containing Protein 4

Network Pharmacology Combined with Machine Learning to Reveal the Action Mechanism of Licochalcone Intervention in Liver Cancer

Ethnopharmacology, chemical composition and functions of Citrus aurantium L

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