The molecular docking and molecular dynamics study of flavonol synthase and flavonoid 3’-monooxygenase enzymes involved for the enrichment of kaempferol

Kumari, Garima; Nigam, Vinod Kumar; Pandey, Dev Mani

doi:10.1080/07391102.2022.2033324

Cited by 15 publications

(11 citation statements)

References 66 publications

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“…We, therefore, investigated if the positive solvation energy resulted due to biases with the MM-GBSA predictor or are true predictions. Indeed, we identified two studies with positive solvation energies calculated by the same MM-GBSA method on different complex systems (93,132). These data suggest that the construct may be soluble after all.…”

Section: Discussionmentioning

confidence: 86%

Rational design of a novel multi-epitope peptide-based vaccine against Onchocerca volvulus using transmembrane proteins

Shey¹,

Ghogomu²,

Nebangwa³

et al. 2022

Front. Trop. Dis

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Almost a decade ago, it was recognized that the global elimination of onchocerciasis by 2030 will not be feasible without, at least, an effective prophylactic and/or therapeutic vaccine to complement chemotherapy and vector control strategies. Recent advances in computational immunology (immunoinformatics) have seen the design of novel multi-epitope onchocerciasis vaccine candidates which are however yet to be evaluated in clinical settings. Still, continued research to increase the pool of vaccine candidates, and therefore the chance of success in a clinical trial remains imperative. Here, we designed a multi-epitope vaccine candidate by assembling peptides from 14 O. volvulus (Ov) proteins using an immunoinformatics approach. An initial 126 Ov proteins, retrieved from the Wormbase database, and at least 90% similar to orthologs in related nematode species of economic importance, were screened for localization, presence of transmembrane domain, and antigenicity using different web servers. From the 14 proteins retained after the screening, 26 MHC-1 and MHC-II (T-cell) epitopes, and linear B-lymphocytes epitopes were predicted and merged using suitable linkers. The Mycobacterium tuberculosis Resuscitation-promoting factor E (RPFE_MYCTU), which is an agonist of TLR4, was then added to the N-terminal of the vaccine candidate as a built-in adjuvant. Immune simulation analyses predicted strong B-cell and IFN-γ based immune responses which are necessary for protection against O. volvulus infection. Protein-protein docking and molecular dynamic simulation predicted stable interactions between the 3D structure of the vaccine candidate and human TLR4. These results show that the designed vaccine candidate has the potential to stimulate both humoral and cellular immune responses and should therefore be subject to further laboratory investigation.

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Section: Discussionmentioning

confidence: 86%

Rational design of a novel multi-epitope peptide-based vaccine against Onchocerca volvulus using transmembrane proteins

Shey¹,

Ghogomu²,

Nebangwa³

et al. 2022

Front. Trop. Dis

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“…The root mean square fluctuation (RMSF) of every amino acid residue is probably the most significant factor determining the ligand stability in the active site of target proteins [ 39 ]. The flexibility within the docked complexes was investigated to track the fluctuations of the residues.…”

Section: Resultsmentioning

confidence: 99%

Investigating Potential Cancer Therapeutics: Insight into Histone Deacetylases (HDACs) Inhibitions

Ahmad,

Saeed,

Al-Amery

et al. 2024

Pharmaceuticals

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Histone deacetylases (HDACs) are enzymes that remove acetyl groups from ɛ-amino of histone, and their involvement in the development and progression of cancer disorders makes them an interesting therapeutic target. This study seeks to discover new inhibitors that selectively inhibit HDAC enzymes which are linked to deadly disorders like T-cell lymphoma, childhood neuroblastoma, and colon cancer. MOE was used to dock libraries of ZINC database molecules within the catalytic active pocket of target HDACs. The top three hits were submitted to MD simulations ranked on binding affinities and well-occupied interaction mechanisms determined from molecular docking studies. Inside the catalytic active site of HDACs, the two stable inhibitors LIG1 and LIG2 affect the protein flexibility, as evidenced by RMSD, RMSF, Rg, and PCA. MD simulations of HDACs complexes revealed an alteration from extended to bent motional changes within loop regions. The structural deviation following superimposition shows flexibility via a visual inspection of movable loops at different timeframes. According to PCA, the activity of HDACs inhibitors induces structural dynamics that might potentially be utilized to define the nature of protein inhibition. The findings suggest that this study offers solid proof to investigate LIG1 and LIG2 as potential HDAC inhibitors.

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“…Previous studies ( Lukacin et al., 2003 ; Shen et al., 2006 ) have shown that the enzymes regulating the hydroxylation at position 3 in the flavonoid biosynthesis pathway primarily include flavanone 3-dioxygenase (1.14.11.9) and flavonol synthase (1.14.20.6). These enzymes catalyze early steps in the flavonoid biosynthesis pathway and require Fe2+ and ascorbate as cofactors ( Xiong et al., 2016 ; Kumari et al., 2023 ). Therefore, it is hypothesized that the A. roxburghii in bamboo and broadleaf environments may be influenced by different iron ion levels or endophytic fungal types in their respective habitats.…”

Section: Discussionmentioning

confidence: 99%

Untargeted metabolomics in Anectocillus roxburghii with habitat heterogeneity and the key abiotic factors affecting its active ingredients

Lyu,

Diao,

et al. 2024

Front. Plant Sci.

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IntroductionAnoectochilus roxburghii is a rare, endangered herb with diverse pharmacological properties. Understanding the main metabolite types and characteristics of wild A. roxburghii is important for efficiently utilizing resources and examining quality according to origin.MethodsSamples were collected from the main production areas across five regions in Fujian Province, China. An untargeted metabolomics analysis was performed on the entire plants to explore their metabolic profiles. We utilized UPLC-MS/MS to specifically quantify eight targeted flavonoids in these samples. Subsequently, correlation analysis was conducted to investigate the relationships between the flavonoids content and both the biological characteristics and geographical features.ResultsA comprehensive analysis identified a total of 3,170 differential metabolites, with terpenoids and flavonoids being the most prevalent classes. A region-specific metabolite analysis revealed that the Yongchun (YC) region showed the highest diversity of unique metabolites, including tangeretin and oleanolic acid. Conversely, the Youxi (YX) region was found to have the smallest number of unique metabolites, with only one distinct compound identified. Further investigation through KEGG pathway enrichment analysis highlighted a significant enrichment in pathways related to flavonoid biosynthesis. Further examination of the flavonoid category showed that flavonols were the most differentially abundant. We quantified eight specific flavonoids, finding that, on average, the YX region exhibited higher levels of these compounds. Correlation analysis highlighted a significant association between flavonoids and habitat, especially temperature and humidity.DiscussionUntargeted metabolomics via LC-MS was suitable for identifying region-specific metabolites and their influence via habitat heterogeneity. The results of this study serve as a new theoretical reference for unique markers exclusively present in a specific sample group.

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The molecular docking and molecular dynamics study of flavonol synthase and flavonoid 3’-monooxygenase enzymes involved for the enrichment of kaempferol

Abstract: Supplementary figure-1:-Ramachandran plot analysis of (a) flavonol synthase and (a') flavonoid 3'monooxygenase (a) (a')

Cited by 15 publications

References 66 publications

Rational design of a novel multi-epitope peptide-based vaccine against Onchocerca volvulus using transmembrane proteins

Rational design of a novel multi-epitope peptide-based vaccine against Onchocerca volvulus using transmembrane proteins

Investigating Potential Cancer Therapeutics: Insight into Histone Deacetylases (HDACs) Inhibitions

Untargeted metabolomics in Anectocillus roxburghii with habitat heterogeneity and the key abiotic factors affecting its active ingredients

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