The Constituents of Honey Propolis is a Boon for Alzheimer's Disease: A Computational Approach

Posted: 7 Feb 2020

See all articles by Md. Junaid

Md. Junaid

Molecular Modeling Drug-design and Discovery Laboratory, BCSIR Laboratories, Chattogram

Syeda Samira Afrose

University of Chittagong

Muhammad Shaiful Alam

Molecular Modeling Drug-design and Discovery Laboratory, BCSIR Laboratories, Chattogram

Yeasmin Akter

Noakhali Science & Technology University

Afsana Nahrin

University of Science and Technology Chittagong

Tania Sharmin

Molecular Modeling Drug-design and Discovery Laboratory, BCSIR Laboratories, Chattogram

Rasheda Akter

Molecular Modeling Drug-design and Discovery Laboratory, BCSIR Laboratories, Chattogram

S. M. Zahid Hosen

University of New South Wales

Date Written: January 15, 2020

Abstract

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

Suggested Citation

Junaid, Md. and Afrose, Syeda Samira and Alam, Muhammad Shaiful and Akter, Yeasmin and Nahrin, Afsana and Sharmin, Tania and Akter, Rasheda and Hosen, S. M. Zahid, The Constituents of Honey Propolis is a Boon for Alzheimer's Disease: A Computational Approach (January 15, 2020). Proceedings of International Conference on Drug Discovery (ICDD) 2020, Available at SSRN: https://ssrn.com/abstract=3531457

Md. Junaid (Contact Author)

Molecular Modeling Drug-design and Discovery Laboratory, BCSIR Laboratories, Chattogram ( email )

Baluchara, Chattogram Cantonment.
Chattogram, 4220
Bangladesh

Syeda Samira Afrose

University of Chittagong ( email )

Chittagong University Rd, Hathazari.
Chattogram, 4331
Bangladesh

Muhammad Shaiful Alam

Molecular Modeling Drug-design and Discovery Laboratory, BCSIR Laboratories, Chattogram ( email )

Baluchara, Chattogram Cantonment, Chattogram 4220
Chattogram, 4220
Bangladesh

Yeasmin Akter

Noakhali Science & Technology University ( email )

Sonapur, University Rd, 3814
Noakhali, 3814
Bangladesh

Afsana Nahrin

University of Science and Technology Chittagong ( email )

Zakir Hossain Road, Foy’s Lake.
Chattogram, 4202
Bangladesh

Tania Sharmin

Molecular Modeling Drug-design and Discovery Laboratory, BCSIR Laboratories, Chattogram ( email )

Baluchara, Chattogram Cantonment, Chattogram 4220
Chattogram, 4220
Bangladesh

Rasheda Akter

Molecular Modeling Drug-design and Discovery Laboratory, BCSIR Laboratories, Chattogram ( email )

Baluchara, Chattogram Cantonment, Chattogram 4220
Chattogram, 4220
Bangladesh

S. M. Zahid Hosen

University of New South Wales ( email )

Liverpool, New South Wales 2170
Australia

Here is the Coronavirus
related research on SSRN

Paper statistics

Abstract Views
718
PlumX Metrics