Mots-Clés
Parametrization
Force Field
Neonicotinoids
CHARMM
Molecular Dynamic
Description
Master internship (5/6 months)—Computational Chemistry
Title of the internship:
Development of CHARMM force field compatible set of parameters to study neonicotinoids with molecular dynamics.
Hosting structure:
Lab name: CEISAM
Head of the lab: Jean-Michel Bouler
Internship intended for students of:
Master 1 & 2
Persons in charge of the internship:
Name : Jean-Yves Le Questel & Zakaria Bouchouireb
Phone : 02 51 12 55 63
E-mail : Jean-Yves.Le-Questel@univ-nantes.fr
E-mail : Zakaria.Bouchouireb@univ-nantes.fr
Description of the internship:
Neonicotinoids are a class of synthetic insecticides that are widely used in agriculture to protect a range of crops from pests. As potent agonists, they act selectively on insect nicotinic acetylcholine receptors (nAChRs), their molecular target site. Mainly claimed as harmless for non-targeted organisms such as pollinators (e.g. honey bees) and mammals, concerns about resistance and toxicity for mammals and the environment have been raised and studied experimentally and with theoretical tools such as docking and classical molecular dynamics (MD)[1,2]. However the bulk of these theoretical studies rely on parameters of poor quality, making their relevance questionable.
In this study, the internship will focus on the development of point charges and bonded parameters for a limited set of neonicotinoids (Fig 1) in order to be used with the additive CHARMM General Force Field (CGenFF)[3]. Once these parameters developed and their quality assessed, we will proceed to study the interactions of the parametrized neonicotinoids with different insects’ nAChRs models.
[1] Ihara, M.; Matsuda, K. Neonicotinoids: Molecular Mechanisms of Action, Insights into Resistance and Impact on Pollinators. Current Opinion in Insect Science, 2018, 30, 86‑92. https://doi.org/10.1016/j.cois.2018.09.009.
[2] Shuai, J.; Wang, X.; Li, G.; Kong, Y.; Li, W.; Li, Z.; Cheng, J. Study on the Mode of Action between Apis Mellifera (Α8)2(Β1)3 NAChR and Typical Neonicotinoids versus Flupyradifurone with Different Bee-Toxic Levels. Journal of Molecular Graphics and Modelling, 2022, 114, 108177. https://doi.org/10.1016/j.jmgm.2022.108177.
[3] Vanommeslaeghe, K.; Hatcher, E.; Acharya, C.; Kundu, S.; Zhong, S.; Shim, J.; Darian, E.; Guvench, O.; Lopes, P.; Vorobyov, I.; Mackerell, A. D., Jr. CHARMM General Force Field: A Force Field for Drug-like Molecules Compatible with the CHARMM All-Atom Additive Biological Force Fields. Journal of Computational Chemistry, 2009, NA-NA. https://doi.org/10.1002/jcc.21367.
Figure 1: Neonicotinoids of interest.
The student will exclusively do computational chemistry and mainly focus on the parameterization process. This will require the use of several software ranging from molecular mechanics to quantum chemistry toolkits deployed on a UNIX environment. In addition, data processing and analysis will require the use of some scripting language such as python or bash. Thus, the student should be at ease with concepts of molecular interactions and the basic physical laws governing them, have some experience in molecular modeling and programming, and be highly motivated to work with a wide range of theory levels and software packages.
This internship will take place as part of the EVALSUB project funded by the ANSES (Agence nationale de sécurité sanitaire de l’alimentation, de l’environnement et du travail) agency and developed between the ModES (Modélisation Et Spectroscopie) team from CEISAM lab (UMR CNRS 6230) and the LBLGC (Laboratoire de Biologie des Ligneux et des Grandes Cultures) lab.
A financial support for a MENRT PhD funding starting in October 2023 will be available within the same scientific context.
If interested, please send an email providing your resume and a motivation letter.