Noncovalent binding of carbofuran to acetylcholinesterase from Homo sapiens, Danio rerio, Apis mellifera and Caenorhabditis elegans: Homology modelling, molecular docking and dynamics, and quantum biochemistry description

Chem Biol Interact. 2023 Dec 13:110826. doi: 10.1016/j.cbi.2023.110826. Online ahead of print.ABSTRACTAlthough various regulatory agencies have banned or severely restricted the use of carbofuran (CAR), recent reports indicate the presence of CAR residues in both cultivated and wild areas. This pesticide is a potent inhibitor of acetylcholinesterase (AChE), which acts by preventing the hydrolysis of acetylcholine (ACh). Given the critical role of AChE::ACh in the proper functioning of the nervous system, we thought it appropriate to investigate the binding of CAR to AChEs from Homo sapiens, Danio rerio, Apis mellifera, and Caenorhabditis elegans using homology modelling, molecular docking, molecular dynamics, and quantum biochemistry. Molecular docking and dynamics results indicated peculiar structural behavior in each AChE::CAR system. Quantum biochemistry results showed similar affinities for all complexes, confirming the description of carbofuran as a broad-spectrum pesticide, and have a limited correlation with IC50 values. We found the following decreasing affinity order of AChE species: H. sapiens > A. mellifera > C. elegans > D. rerio. The computational results suggest that CAR occupies different pockets in the AChEs studied. In addition, our results showed that CAR binds to hsAChE and ceAChE in a very similar manner: it has high affinities for the same subsites in both species and forms hydrogen bonds with residues (hsTYR124 and ceTRP107) occupying homologous...
Source: Chemico-Biological Interactions - Category: Molecular Biology Authors: Source Type: research