Publication: MOLECULAR DYNAMICS SIMULATION OF ORIENTIN ON BETA-AMYLOID BIOSYNTHESIS ENZYME-BACE1
Date
2023
Authors
Journal Title
Journal ISSN
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Publisher
International Medical University
Abstract
Alzheimer’s disease is a neurodegenerative disease that encounters more than half of the elderly
population worldwide. The existing Alzheimer’s disease drugs are associated with limitations that
warrant the discovery of novel drugs. Previous studies suggested orientin could be the potential
Alzheimer’s disease therapeutic agent due to its neuroprotective, antioxidant, and anti-
inflammatory properties. In this study, molecular dynamics simulations were performed to study
and compare the binding patterns of orientin and the control ligand, MY9. AmberTools22 was
used to perform molecular dynamics simulations. The 3D structure of BACE1 was retrieved from
Protein Data Bank. Two stages of minimization were performed to remove the steric hindrance of
the starting structure. The simulation started with heating up to 300 K, followed by the
equilibration stage, and finally data collection for 50 ns. Thermodynamic properties were
monitored throughout the simulation time and structural analysis was performed to analyse the
conformation changes of the simulation systems. As the result, all simulation systems are stable
throughout the simulation time and the result of the structural analysis indicates that the complex
is stable as no significant deviation is detected in the analysis output. The binding interaction of
orientin to BACE1 stabilised by hydrogen bond interaction is favourable, although it is weaker
compared to MY9 and the compactness is similar to the BACE1-MY9 complex, indicating
favourable binding interaction. Lastly, orientin binding also induces lesser conformation changes
to BACE1 due to higher solvent accessibility. In accordance with the comparative analysis, it can
be concluded that orientin has better therapeutic potential compared to MY9 which depicted the
significance of orientin as a novel therapeutic approach in molecular dynamics treatment.
Keywords: Alzheimer’s disease, orientin, BACE1, beta-amyloid biosynthesis, molecular
dynamics simulation
Description
Keywords
Alzheimer Disease, Molecular Dynamics Simulation, Aged, Neurodegenerative Diseases, Neurofibrillary Tangles