title: Insight into the Binding Mode of Agonists of the Nicotinic Acetylcholine Receptor from Calculated Electron Densities.
abstract: Insect nicotinic acetylcholine receptors (nAChRs) are among the most prominent and most economically important insecticide targets. Thus, an understanding of the modes of binding of respective agonists is important for the design of specific compounds with favorable vertebrate profiles. In the case of nAChRs, the lack of available high-resolution X-ray structures leaves theoretical considerations as the only viable option. Starting from classical homology and docking approaches, binding mode hypotheses are created for five agonists of the nAChR, covering insecticides in the main group 4 of the Insecticide Resistance Action Committee (IRAC) mode of action (MoA) classification, namely, neonicotinoids, nicotine, sulfoxaflor, and butenolides. To better understand these binding modes, the topologies of calculated electron densities of small-model systems are analyzed in the framework of the quantum theory of atoms in molecules. The theoretically obtained modes of binding are very much in line with the biology-driven IRAC MoA classification of the investigated ligands.
authors.affiliation: Head of Computational Science, Bayer CropScience AG, R&D-SMR-RT-Computational Science, Alfred-Nobel-Strasse 50, 40789 Monheim am Rhein (Germany).
authors.forename: Michael E
authors.initials: ME
authors.lastname: Beck
authors.affiliation: Molecular Modelling, Bayer CropScience AG, R&D-SMR-RT-Computational Science, Alfred-Nobel-Strasse 50, 40789 Monheim am Rhein (Germany).
authors.forename: Oliver
authors.initials: O
authors.lastname: Gutbrod
authors.affiliation: Molecular Modelling, Bayer CropScience AG, R&D-SMR-RT-Computational Science, Alfred-Nobel-Strasse 50, 40789 Monheim am Rhein (Germany).
authors.forename: Svend
authors.initials: S
authors.lastname: Matthiesen
keywords: density functional calculations; ion channels; molecular modeling; protein models; quantum chemistry