In silico, theoretical biointerface analysis and in vitro kinetic analysis of amine compounds interaction with acetylcholinesterase and butyrylcholinesterase

Kandasamy, S and Loganathan, C and Sakayanathan, P and Karthikeyan, S and Stephen, AD and Marimuthu, DK and Ravichandran, S and Sivalingam, V and Thayumanavan, P (2021) In silico, theoretical biointerface analysis and in vitro kinetic analysis of amine compounds interaction with acetylcholinesterase and butyrylcholinesterase. In: International Journal of Biological Macromolecules, 185 . pp. 750-760.

	PDF int_jou_bio_mac_185_750-760_2021.pdf - Published Version Restricted to Registered users only Download (2MB) | Request a copy
	Microsoft Word 1-s2.0-S0141813021014045-mmc1.docx - Published Supplemental Material Restricted to Registered users only Download (11MB) | Request a copy

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 non-covalent 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. © 2021

Item Type:	Journal Article
Publication:	International Journal of Biological Macromolecules
Publisher:	Elsevier B.V.
Additional Information:	The copyright for this article belongs to Elsevier B.V.
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	14 Sep 2021 11:27
Last Modified:	14 Sep 2021 11:27
URI:	http://eprints.iisc.ac.in/id/eprint/69590

Actions (login required)

View Item