Discovery of new potential triplet acting inhibitor for Alzheimer’s disease via X-ray crystallography, molecular docking and molecular dynamics
| Autor: | Kandasamy Saravanan, Maharajan Sivakumar, Velautham Saravanan, Mustafa Alhaji Isa, Srinivasan Sugarthi, Perumal Rajakumar, Shankar Madan Kumar, S. Aravindhan |
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| Rok vydání: | 2019 |
| Předmět: |
0303 health sciences
Chemistry musculoskeletal neural and ocular physiology 030303 biophysics macromolecular substances General Medicine Disease Computational biology Molecular Dynamics Simulation Crystallography X-Ray medicine.disease Molecular Docking Simulation 03 medical and health sciences Molecular dynamics nervous system Alzheimer Disease Structural Biology medicine Humans Dementia Molecular Biology Protein Binding |
| Zdroj: | Journal of Biomolecular Structure and Dynamics. 38:1903-1917 |
| ISSN: | 1538-0254 0739-1102 |
| DOI: | 10.1080/07391102.2019.1620128 |
| Popis: | The most common brain disorder of late life is Alzheimer's disease (AD), which is highly complicating dementia. There are several drug targets which are reported to control the severe level of AD; notably, acetylcholinesterase, β-Secretase and glycogen synthase kinase enzymes are approached as a good drug targets for AD. Hence, the present study mainly focused to discover newly synthesized molecule (7-propyl-6H-pyrano[3,2-c:5,6-c']dichromene-6,8(7H)-dione) as a potential triplet acting drug for above said enzymes through the analysis of X-ray crystallography, molecular docking, molecular dynamics and quantum chemical calculation. The target drug molecule was crystallized in the monoclinic crystal structure with P21/n space group. The structure was solved by SHELXS and refined by SHELXL. The crystal packing is stabilized by C - H···O type of interactions. Further, the induced fit docking shows that the molecule has high docking score, glide energy, favorable hydrogen bonding and hydrophobic interactions on the protein targets. The molecular dynamics simulation was performed to understand the stability of the molecule in the presence of active site environment. Finally, quantum chemical calculation has been carried out for the molecule in gas phase and for the corresponding molecule lifted from the active site region. The structural comparison between gas phase and active site helps to understand the conformational modification of the molecule in the active site. Communicated by Ramaswamy H. Sarma. |
| Databáze: | OpenAIRE |
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