In-silico and in-vitro evaluation of human acetylcholinesterase inhibition by organophosphates

In Silico Study of the Resistance to Organophosphorus Pesticides Associated with Point Mutations in Acetylcholinesterase of Lepidoptera: B. mandarina, B. mori, C. auricilius, C. suppressalis, C. pomonella, H. armígera, P. xylostella, S. frugiperda, and S. litura

“…The computational methodology was verified by comparing our results of the binding energy (Δ G b ) predicted with the docking results reported previously (see Appendix B) by Somani et al (2015) to AChE of humans in complex with psoralen (PDB 1EVE was used) [22] and Ranjan et al (2018) to AChE of humans in complex with several ligands (PDB 3LII was used) [38]; phosalone (CID6199), dimefox (CID8264), dichlorvos (CID5371560), phoxim ethyl phosphonate (CID6507160), heptenophos (CID62773), and methamidophos (CID4096). These molecules were obtained from the PubChem database [36,37].…”

“…The verification of computational methodology consisted of reproducing results of Δ G b , previously reported by Ranjan et al 2018 [38], Somani et al 2015 [22], Chaudhry et al 2013 [42], and Sharma et al 2011 [43] approaches the interaction of OP with human AChE, where these authors use crystallographic structures to perform their analyses. In order to detect the variability in reproducibility in energy prediction, we evaluated 28 OPs molecules using our methodology (results not shown).…”

“…In order to detect the variability in reproducibility in energy prediction, we evaluated 28 OPs molecules using our methodology (results not shown). We detected (performing 10 runs, in accordance with the docking protocol for the Autodoc 4.2) program variations in the determination of Δ G b of 0.5 Kcal/mol; this parameter was obtained by analyzing the variation in the results of the evaluations of the 28 OPs.The Δ G b predictions obtained by docking with the purpose of comparing the computational protocol with other computational methodology reporters, in which six molecules on human AChE (PDB: 1EVE) were evaluated, provided results according to those previously reported [22,38] by other research groups (see Table A2). The docking study performed by Somani et al (2015) and Ranjan et al (2018) was carried out using the standard glide molecular docking protocol implemented within the Maestro molecular modeling suite by Schrodinger [22,38].…”

“…The Δ G b predictions obtained by docking with the purpose of comparing the computational protocol with other computational methodology reporters, in which six molecules on human AChE (PDB: 1EVE) were evaluated, provided results according to those previously reported [22,38] by other research groups (see Table A2). The docking study performed by Somani et al (2015) and Ranjan et al (2018) was carried out using the standard glide molecular docking protocol implemented within the Maestro molecular modeling suite by Schrodinger [22,38]. The results register a relative binding energy (ΔΔ G b ) with a value up to −1.42 Kcal/mol.…”

Combining In Silico and In Vitro Studies to Evaluate the Acetylcholinesterase Inhibitory Profile of Different Accessions and the Biomarker Triterpenes of Centella asiatica

“…Molecular docking is a tool in computer aided drug designing (CADD) which is used to study the binding interaction between the potential inhibitors, known as ligands, and targeted enzymes [24]. The X-ray crystal structures of AChE from various species can be found in the protein data bank (PDB) [25]. The identification of residues that are responsible for inhibitory activity will lead to potential for the synthesis of agents with a high efficacy of biological action [26].…”