In silico, theoretical biointerface analysis and in vitro kinetic analysis of amine compounds interaction with acetylcholinesterase and butyrylcholinesterase
| Autor: | Dinesh Kumar Marimuthu, Palvannan Thayumanavan, Penislusshiyan Sakayanathan, Arputharaj David Stephen, Vignesh Sivalingam, Saravanan Kandasamy, Subramani Karthikeyan, Saravanan Ravichandran, Chitra Loganathan |
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| Rok vydání: | 2021 |
| Předmět: |
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Molecular Stereochemistry In silico Drug Evaluation Preclinical Molecular Conformation Biointerface 02 engineering and technology Molecular Dynamics Simulation Crystallography X-Ray Biochemistry 03 medical and health sciences chemistry.chemical_compound Structure-Activity Relationship Structural Biology Humans Computer Simulation Amines Molecular Biology Butyrylcholinesterase 030304 developmental biology 0303 health sciences Virtual screening Binding Sites biology Chemistry Active site General Medicine 021001 nanoscience & nanotechnology Ligand (biochemistry) Acetylcholinesterase Molecular Docking Simulation Kinetics biology.protein Amine gas treating Cholinesterase Inhibitors 0210 nano-technology |
| Zdroj: | International journal of biological macromolecules. 185 |
| ISSN: | 1879-0003 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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