The Constituents of Honey Propolis is a Boon for Alzheimer's Disease: A Computational Approach
Posted: 7 Feb 2020
Date Written: January 15, 2020
Alzheimer’s disease (AD) is one of the most common neurodegenerative disorders showing slow progressive cognitive decline. Focusing on acetylcholinesterase (AChE) is one of the significant tactics for AD therapeutics, as cholinergic pathways in the cerebral cortex and basal forebrain are undermined. Propolis, a substance naturally produced by bees upon an assortment of plant resins, is used in traditional medication for its useful activity. A recent study claims that propolis has good anti-Alzheimer’s activity. Regarding this concern, we made a full library database of honey propolis constituents up to November 2019 and screened that database constituents against human AChE target with several computational techniques. At first, we collect all constituents’ 3D structures in sdf format from different small molecules databases and unavailable structures were sketched by ChemDraw and also converted them into sdf format. After that, we collect Donepezil bound human AChE protein id (4ey7) from the protein data bank. We optimized our all constituents in Ligprep wizard, by implementing OPLS3e force field and at the same time we performed the energy minimization process by Protein Preparation Wizard with the same force field for protein. In order to check the binding modes of compounds against AChE, molecular docking simulations by extra precision (XP) flexible docking using the Glide module of Schrödinger-Maestro v11.6 were performed. For investigating the binding free energy the best docking score (lowest energy value) of ligand-protein has been calculated, where low energy values ensure high binding affinity. Specific interactions have also been investigated to understand the nature of intermolecular bonds between the most active ligands and the amino acid residues of protein binding sites. In order to understand the structural conformation changes i.e. dynamic stability and flexibility, binding mechanism, and evaluate the interactions of the ligand molecules with the AChE, we carried out MD simulation for best candidates protein-ligand complexes. As a reference compound, the complex of donepezil-AChE was also subjected to MD simulation. Both Docking and MD simulation has disclosed that the honey propolis constituents are more potent, stable and superior to the control inhibitor and represent potentially interesting scaffolds for further in vitro biological evaluation and anti-Alzheimer’s drug design.
Keywords: Alzheimer’s Disease, Acetylcholinesterase, Honey Propolis, Schrödinger-Maestro v11.6, XP Docking, Molecular Dynamics
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