Publication: MOLECULAR DYNAMICS SIMULATION OF HYPERPHOSPHORYLATED TAU PROTEIN WITH POTENTIAL LIGANDS FROM DRUG REPURPOSING
| dc.contributor.author | KEE KYE VERN | |
| dc.date.accessioned | 2023-10-06T14:25:17Z | |
| dc.date.available | 2023-10-06T14:25:17Z | |
| dc.date.issued | 2022 | |
| dc.description.abstract | Alzheimer disease (AD) is a progressive degenerative disorder of the brain resulting in the loss of higher cognitive function and is considered as the most common form of dementia. AD is characterised by a triad of pathological changes in the brain and there have been many proposed approaches and research aimed at treating AD. The two hallmark substrates causing the cognitive decline in AD are the amyloid beta (Aβ) plaques deposition, and the neurofibrillary tangles of hyperphosphorylated (HP) tau. In recent years, the focus on research has been based on the Aβ hypothesis. However, the failed clinical drug trials targeting Aβ suggest that tau related therapies may be a more viable approach to AD treatment. This study aims to analyse the binding affinity of Teniposide and Testosterone Enanthate as potential repurposed drug candidates acting as aggregation inhibitors of HP tau protein to prevent the formation of neurofibrillary tangles (NFT) which might stop the progression of AD. The binding interactions between the two proposed drugs with the HP tau protein was analysed by conducting 20 ns molecular dynamics (MD) simulation. Thermodynamics properties, root mean squared deviation (RMSF), root mean squared fluctuation (RMSF), radius of gyration (RoG) and hydrogen bond (HB) analysis were conducted on the trajectories of the MD simulation. The findings from this study suggested that Teniposide is the better potential compound in inhibiting the aggregation of HP tau protein and should be analysed further with a longer simulation, inclusion of MMGB/PBSA calculation and 2D/3D interaction images to ensure higher reliability. | en_US |
| dc.identifier.uri | https://hdl.handle.net/20.500.14377/31954 | |
| dc.language.iso | en | en_US |
| dc.publisher | International Medical University | en_US |
| dc.subject | Alzheimer Disease | en_US |
| dc.subject | Teniposide | en_US |
| dc.subject | Testosterone | en_US |
| dc.subject | Neurofibrillary Tangles | en_US |
| dc.title | MOLECULAR DYNAMICS SIMULATION OF HYPERPHOSPHORYLATED TAU PROTEIN WITH POTENTIAL LIGANDS FROM DRUG REPURPOSING | en_US |
| dc.type | Thesis | |
| dspace.entity.type | Publication |