title: Molecular recognition of thiaclopride by Aplysia californica AChBP: new insights from a computational investigation.
abstract: 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···π/CH···O and π-π stacking interactions, respectively. These trends are confirmed through a complementary non-covalent interaction (NCI) analysis of selected THI-Ac-AChBP amino acid pairs.
authors.affiliation: CEISAM UMR CNRS 6230, Faculté des Sciences et des Techniques, Université de Nantes, 2 rue de la Houssinière, BP 92208, Nantes, 44322, France.
authors.forename: Zakaria
authors.initials: Z
authors.lastname: Alamiddine
authors.affiliation: CEISAM UMR CNRS 6230, Faculté des Sciences et des Techniques, Université de Nantes, 2 rue de la Houssinière, BP 92208, Nantes, 44322, France.|Roger Adams Laboratory, University of Illinois at Urbana-Champaign, 600 S Mathews Ave, Urbana, IL, 61801, USA.
authors.forename: Balaji
authors.initials: B
authors.lastname: Selvam
authors.affiliation: CEISAM UMR CNRS 6230, Faculté des Sciences et des Techniques, Université de Nantes, 2 rue de la Houssinière, BP 92208, Nantes, 44322, France.|Bioinformatics and High Performance Computing Research Group (BIO-HPC), Computer Science Department, Universidad Católica San Antonio de Murcia (UCAM), Campus de los Jerónimos, 30107, Murcia, Spain.
authors.forename: José P
authors.initials: JP
authors.lastname: Cerón-Carrasco
authors.affiliation: CEISAM UMR CNRS 6230, Faculté des Sciences et des Techniques, Université de Nantes, 2 rue de la Houssinière, BP 92208, Nantes, 44322, France.
authors.forename: Monique
authors.initials: M
authors.lastname: Mathé-Allainmat
authors.affiliation: CEISAM UMR CNRS 6230, Faculté des Sciences et des Techniques, Université de Nantes, 2 rue de la Houssinière, BP 92208, Nantes, 44322, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Lebreton
authors.affiliation: Laboratoire de Biologie des Ligneux et des Grandes Cultures, Université d'Orléans, UPRES EA 1207. Rue de Chartres, BP 6759, 45067, Orléans Cedex 2, France.
authors.forename: Steeve H
authors.initials: SH
authors.lastname: Thany
authors.affiliation: CEISAM UMR CNRS 6230, Faculté des Sciences et des Techniques, Université de Nantes, 2 rue de la Houssinière, BP 92208, Nantes, 44322, France.
authors.forename: Adèle D
authors.initials: AD
authors.lastname: Laurent
authors.affiliation: CEISAM UMR CNRS 6230, Faculté des Sciences et des Techniques, Université de Nantes, 2 rue de la Houssinière, BP 92208, Nantes, 44322, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Graton
authors.affiliation: CEISAM UMR CNRS 6230, Faculté des Sciences et des Techniques, Université de Nantes, 2 rue de la Houssinière, BP 92208, Nantes, 44322, France. Jean-Yves.Le-Questel@univ-nantes.fr.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Le Questel
mesh_terms: D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001048:Aplysia / Q000187:drug effects* / Q000378:metabolism*; D001665:Binding Sites; D006860:Hydrogen Bonding; D007093:Imidazoles / Q000737:chemistry / Q000378:metabolism; D007306:Insecticides / Q000737:chemistry / Q000378:metabolism*; D062105:Molecular Docking Simulation; D000073943:Neonicotinoids; D009574:Nitro Compounds / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011789:Quantum Theory; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D000596:Amino Acids; D007093:Imidazoles; D007306:Insecticides; D000073943:Neonicotinoids; D009574:Nitro Compounds; D011978:Receptors, Nicotinic; C082359:imidacloprid
keywords: AChBP; Neonicotinoids; ONIOM calculations; Thiacloprid