David Stephen, A (2021) In silico, theoretical biointerface analysis and in vitro kinetic analysis of amine compounds interaction with acetylcholinesterase and butyrylcholinesterase. International Journal of Biological Macromolecules, 185. pp. 750-760. ISSN 0141-8130

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Abstract

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are considered important target for drug design
against Alzheimer's disease. In the present study in silico analysis; theoretical analysis of biointerface between
ligand and interacting amino acid residues of proteins; and in vitro analysis of enzyme inhibition kinetics were
carried out to delineate the inhibitory property of amine compounds against AChE/BChE. High throughput
virtual screening of amine compounds identified three compounds (2-aminoquinoline, 2-aminobenzimidazole
and 2-amino-1-methylbenzimidazole) that best interacted with AChE/BChE. Molecular docking analysis
revealed the interaction of these compounds in the active site gorge of AChE/BChE, in particular with amino acid
residues present in the peripheral anionic site. Molecular dynamics simulation confirmed the stable binding of
these compounds with AChE/BChE. Binding energy calculated through MMGBSA method identified the noncovalent interactions (electrostatic and Van der Waals interactions) have contributed to the stable binding of
the amine compounds with the AChE/BChE. Biointerface between amine compounds and AChE/BChE were
visualized through Hirshfeld surface analysis. The inter-fragment interaction energies for the possible contacts
between amine compounds and amino acid residues were carried out for the first time. All the amine compounds
showed mixed-type of inhibition with moderate Ki value in in vitro analysis.

Item Type: Article
Uncontrolled Keywords: Acetylcholinesterase Butyrylcholinesterase Hirshfeld surface analysis Molecular dynamics simulation Electron density calculation
Depositing User: Mr Team Mosys
Date Deposited: 03 Aug 2022 04:39
Last Modified: 03 Aug 2022 04:39
URI: http://ir.psgcas.ac.in/id/eprint/1396

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