Article Dans Une Revue Journal of Computer-Aided Molecular Design Année : 2015

Molecular recognition of thiaclopride by Aplysia californica AChBP: new insights from a computational investigation

Résumé

The binding of thiaclopride (THI), a neonicotinoid insecticide, with Aplysia californica acetylcholine binding protein (Ac-AChBP), the surrogate of the extracellular domain of insects nicotinic acetylcholine receptors, has been studied with a QM/QM' hybrid methodology using the ONIOM approach (M06-2X/6-311G(d):PM6). The contributions of Ac-AChBP key residues for THI binding are accurately quantified from a structural and energetic point of view. The importance of water mediated hydrogen-bond (H-bond) interactions involving two water molecules and Tyr55 and Ser189 residues in the vicinity of the THI nitrile group, is specially highlighted. A larger stabilization energy is obtained with the THI-Ac-AChBP complex compared to imidacloprid (IMI), the forerunner of neonicotinoid insecticides. Pairwise interaction energy calculations rationalize this result with, in particular, a significantly more important contribution of the pivotal aromatic residues Trp147 and Tyr188 with THI through CH center dot center dot center dot pi/CH center dot center dot center dot O and pi-pi stacking interactions, respectively. These trends are confirmed through a complementary non-covalent interaction (NCI) analysis of selected THI-Ac-AChBP amino acid pairs.

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Dates et versions

hal-01389009 , version 1 (27-10-2016)

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Zakaria Alamiddine, Balaji Selvam, Jose P. Ceron-Carrasco, Monique Mathé-Allainmat, Jacques Lebreton, et al.. Molecular recognition of thiaclopride by Aplysia californica AChBP: new insights from a computational investigation. Journal of Computer-Aided Molecular Design, 2015, 29 (12), pp.1151-1167. ⟨10.1007/s10822-015-9884-x⟩. ⟨hal-01389009⟩
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