The Computational Analysis and Phytochemical Screening Targeting Dihydrolipoamide Dehydrogenase (DLD) for Alzheimer's Disease: A Molecular Dynamics Simulation Study
The decreasing rate of metabolisms within the mitochondrial is connected to the progressive characterization of Alzheimer's Disease (AD). Dihydrolipoamide dehydrogenase (dld), and DLD1 are specific chemicals comprised of two enzymes/complexes of protein; pyruvate dehydrogenase and α-ketoglutara...
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Odv Casa Arcobaleno
2024-07-01
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| Series: | European Journal of Volunteering and Community-Based Projects |
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| author | Muhammad Mazhar Fareed |
| author_facet | Muhammad Mazhar Fareed |
| author_sort | Muhammad Mazhar Fareed |
| collection | DOAJ |
| description | The decreasing rate of metabolisms within the mitochondrial is connected to the progressive characterization of Alzheimer's Disease (AD). Dihydrolipoamide dehydrogenase (dld), and DLD1 are specific chemicals comprised of two enzymes/complexes of protein; pyruvate dehydrogenase and α-ketoglutarate dehydrogenase physiologically related to AD and have a noteworthy function in energy metabolism. The present computational study was designed to envisage a rational screening of natural phytochemical compounds against DLD1 in AD. The molecular docking and virtual screening approaches were adopted within the best binding active sites of DLD1 in AD to screen 15,282 medicinal phytochemicals’ libraries, which were developed from the literature search, PubChem, Zinc Database, and MPD3 Database. This docking followed by MD-simulation of the best three complexes (1-Caffeoyl-4-deoxyquinic acid, N-Butyryl Coenzyme A, Precatorine) determined through docking scores, RMSD-refine, Pharmacokinetics properties, pharmacological analysis, molinspiration, ADMET-properties, and binding energies. The top complexes with docking-S scores (-13.7117, -12.4565, -11.6440), RMSD-refine values (1.64, 0.86, 0.93), and interactive hits/residues (Arg216, Leu263, Ile125, Met262, Asp256), showed a binding affinity with another catalytic active site domain-chain A (residues 86-293). Although this in-silico work is not experimentally determined, the affinity and interactions of these selected novel compounds might help to design the therapeutics against Alzheimer’s Disease.
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| format | Article |
| id | doaj-art-5e4134d831dc4172898ab6a2aadc8a2a |
| institution | OA Journals |
| issn | 2724-0592 2724-1947 |
| language | English |
| publishDate | 2024-07-01 |
| publisher | Odv Casa Arcobaleno |
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| series | European Journal of Volunteering and Community-Based Projects |
| spelling | doaj-art-5e4134d831dc4172898ab6a2aadc8a2a2025-08-20T02:13:24ZengOdv Casa ArcobalenoEuropean Journal of Volunteering and Community-Based Projects2724-05922724-19472024-07-0112The Computational Analysis and Phytochemical Screening Targeting Dihydrolipoamide Dehydrogenase (DLD) for Alzheimer's Disease: A Molecular Dynamics Simulation StudyMuhammad Mazhar Fareed0Government College University FaisalabadThe decreasing rate of metabolisms within the mitochondrial is connected to the progressive characterization of Alzheimer's Disease (AD). Dihydrolipoamide dehydrogenase (dld), and DLD1 are specific chemicals comprised of two enzymes/complexes of protein; pyruvate dehydrogenase and α-ketoglutarate dehydrogenase physiologically related to AD and have a noteworthy function in energy metabolism. The present computational study was designed to envisage a rational screening of natural phytochemical compounds against DLD1 in AD. The molecular docking and virtual screening approaches were adopted within the best binding active sites of DLD1 in AD to screen 15,282 medicinal phytochemicals’ libraries, which were developed from the literature search, PubChem, Zinc Database, and MPD3 Database. This docking followed by MD-simulation of the best three complexes (1-Caffeoyl-4-deoxyquinic acid, N-Butyryl Coenzyme A, Precatorine) determined through docking scores, RMSD-refine, Pharmacokinetics properties, pharmacological analysis, molinspiration, ADMET-properties, and binding energies. The top complexes with docking-S scores (-13.7117, -12.4565, -11.6440), RMSD-refine values (1.64, 0.86, 0.93), and interactive hits/residues (Arg216, Leu263, Ile125, Met262, Asp256), showed a binding affinity with another catalytic active site domain-chain A (residues 86-293). Although this in-silico work is not experimentally determined, the affinity and interactions of these selected novel compounds might help to design the therapeutics against Alzheimer’s Disease. https://localhost/index.php/ejvcbp/article/view/143Alzheimer’s disease, Dihydrolipoamide dehydrogenase (DLD1), Molecular docking, Natural medicinal compounds, MD-simulation, Pharmacokinetics analysis. |
| spellingShingle | Muhammad Mazhar Fareed The Computational Analysis and Phytochemical Screening Targeting Dihydrolipoamide Dehydrogenase (DLD) for Alzheimer's Disease: A Molecular Dynamics Simulation Study European Journal of Volunteering and Community-Based Projects Alzheimer’s disease, Dihydrolipoamide dehydrogenase (DLD1), Molecular docking, Natural medicinal compounds, MD-simulation, Pharmacokinetics analysis. |
| title | The Computational Analysis and Phytochemical Screening Targeting Dihydrolipoamide Dehydrogenase (DLD) for Alzheimer's Disease: A Molecular Dynamics Simulation Study |
| title_full | The Computational Analysis and Phytochemical Screening Targeting Dihydrolipoamide Dehydrogenase (DLD) for Alzheimer's Disease: A Molecular Dynamics Simulation Study |
| title_fullStr | The Computational Analysis and Phytochemical Screening Targeting Dihydrolipoamide Dehydrogenase (DLD) for Alzheimer's Disease: A Molecular Dynamics Simulation Study |
| title_full_unstemmed | The Computational Analysis and Phytochemical Screening Targeting Dihydrolipoamide Dehydrogenase (DLD) for Alzheimer's Disease: A Molecular Dynamics Simulation Study |
| title_short | The Computational Analysis and Phytochemical Screening Targeting Dihydrolipoamide Dehydrogenase (DLD) for Alzheimer's Disease: A Molecular Dynamics Simulation Study |
| title_sort | computational analysis and phytochemical screening targeting dihydrolipoamide dehydrogenase dld for alzheimer s disease a molecular dynamics simulation study |
| topic | Alzheimer’s disease, Dihydrolipoamide dehydrogenase (DLD1), Molecular docking, Natural medicinal compounds, MD-simulation, Pharmacokinetics analysis. |
| url | https://localhost/index.php/ejvcbp/article/view/143 |
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