Study of Caspase 8 Inhibition for the Management of Alzheimer’s Disease: A Molecular Docking and Dynamics Simulation
Alzheimer’s disease (AD) is the most common type of dementia and usually manifests as diminished episodic memory and cognitive functions. Caspases are crucial mediators of neuronal death in a number of neurodegenerative diseases, and caspase 8 is considered a major therapeutic target in the context...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-04-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/9/2071 |
| _version_ | 1797569359936225280 |
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| author | Syed Sayeed Ahmad Meetali Sinha Khurshid Ahmad Mohammad Khalid Inho Choi |
| author_facet | Syed Sayeed Ahmad Meetali Sinha Khurshid Ahmad Mohammad Khalid Inho Choi |
| author_sort | Syed Sayeed Ahmad |
| collection | DOAJ |
| description | Alzheimer’s disease (AD) is the most common type of dementia and usually manifests as diminished episodic memory and cognitive functions. Caspases are crucial mediators of neuronal death in a number of neurodegenerative diseases, and caspase 8 is considered a major therapeutic target in the context of AD. In the present study, we performed a virtual screening of 200 natural compounds by molecular docking with respect to their abilities to bind with caspase 8. Among them, rutaecarpine was found to have the highest (negative) binding energy (−6.5 kcal/mol) and was further subjected to molecular dynamics (MD) simulation analysis. Caspase 8 was determined to interact with rutaecarpine through five amino acid residues, specifically Thr337, Lys353, Val354, Phe355, and Phe356, and two hydrogen bonds (ligand: H35-A: LYS353:O and A:PHE355: N-ligand: N5). Furthermore, a 50 ns MD simulation was conducted to optimize the interaction, to predict complex flexibility, and to investigate the stability of the caspase 8–rutaecarpine complex, which appeared to be quite stable. The obtained results propose that rutaecarpine could be a lead compound that bears remarkable anti-Alzheimer’s potential against caspase 8. |
| first_indexed | 2024-03-10T20:09:42Z |
| format | Article |
| id | doaj.art-a55ebc573c514782878051c4fb8d090f |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T20:09:42Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-a55ebc573c514782878051c4fb8d090f2023-11-19T23:00:57ZengMDPI AGMolecules1420-30492020-04-01259207110.3390/molecules25092071Study of Caspase 8 Inhibition for the Management of Alzheimer’s Disease: A Molecular Docking and Dynamics SimulationSyed Sayeed Ahmad0Meetali Sinha1Khurshid Ahmad2Mohammad Khalid3Inho Choi4Department of Medical Biotechnology, Yeungnam University, Gyeongsan 38541, KoreaDepartment of Bioengineering, Integral University, Lucknow 226026, IndiaDepartment of Medical Biotechnology, Yeungnam University, Gyeongsan 38541, KoreaCollege of Pharmacy, Department of Pharmacognosy, Prince Sattam Bin Abdul Aziz University, Alkharj 16278, Riyadh, Saudi ArabiaDepartment of Medical Biotechnology, Yeungnam University, Gyeongsan 38541, KoreaAlzheimer’s disease (AD) is the most common type of dementia and usually manifests as diminished episodic memory and cognitive functions. Caspases are crucial mediators of neuronal death in a number of neurodegenerative diseases, and caspase 8 is considered a major therapeutic target in the context of AD. In the present study, we performed a virtual screening of 200 natural compounds by molecular docking with respect to their abilities to bind with caspase 8. Among them, rutaecarpine was found to have the highest (negative) binding energy (−6.5 kcal/mol) and was further subjected to molecular dynamics (MD) simulation analysis. Caspase 8 was determined to interact with rutaecarpine through five amino acid residues, specifically Thr337, Lys353, Val354, Phe355, and Phe356, and two hydrogen bonds (ligand: H35-A: LYS353:O and A:PHE355: N-ligand: N5). Furthermore, a 50 ns MD simulation was conducted to optimize the interaction, to predict complex flexibility, and to investigate the stability of the caspase 8–rutaecarpine complex, which appeared to be quite stable. The obtained results propose that rutaecarpine could be a lead compound that bears remarkable anti-Alzheimer’s potential against caspase 8.https://www.mdpi.com/1420-3049/25/9/2071Alzheimer’s diseasecaspase 8molecular dynamicsRMSDRMSF |
| spellingShingle | Syed Sayeed Ahmad Meetali Sinha Khurshid Ahmad Mohammad Khalid Inho Choi Study of Caspase 8 Inhibition for the Management of Alzheimer’s Disease: A Molecular Docking and Dynamics Simulation Molecules Alzheimer’s disease caspase 8 molecular dynamics RMSD RMSF |
| title | Study of Caspase 8 Inhibition for the Management of Alzheimer’s Disease: A Molecular Docking and Dynamics Simulation |
| title_full | Study of Caspase 8 Inhibition for the Management of Alzheimer’s Disease: A Molecular Docking and Dynamics Simulation |
| title_fullStr | Study of Caspase 8 Inhibition for the Management of Alzheimer’s Disease: A Molecular Docking and Dynamics Simulation |
| title_full_unstemmed | Study of Caspase 8 Inhibition for the Management of Alzheimer’s Disease: A Molecular Docking and Dynamics Simulation |
| title_short | Study of Caspase 8 Inhibition for the Management of Alzheimer’s Disease: A Molecular Docking and Dynamics Simulation |
| title_sort | study of caspase 8 inhibition for the management of alzheimer s disease a molecular docking and dynamics simulation |
| topic | Alzheimer’s disease caspase 8 molecular dynamics RMSD RMSF |
| url | https://www.mdpi.com/1420-3049/25/9/2071 |
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