Study the interaction of dinotefuran with human cytochrome P450 1A1 (CYP1A1) using molecular docking, molecular dynamics simulations and DFT calculations

Dinotefuran is a neonicotinoid insecticide widely used in agriculture that shows high insecticidal efficacy, rapid plant absorption, and potential for environmental contamination due to its water solubility. Yet its interactions with human metabolic enzymes remain poorly understood. Human cytochrome P450 1A1 (CYP1A1) is an enzyme involved in the metabolism of xenobiotics and endogenous compounds including polycyclic aromatic hydrocarbons and therapeutic drugs. This study investigates the molecular interaction of dinotefuran with human cytochrome P450 1A1 (PDB ID: 4I8V) using molecular docking, molecular dynamics (MD) simulations, and density functional theory (DFT). Docking results shows a binding energy of -6.3 kcal/mol highlighting strong interactions with key residues. MD simulations showed the dynamic stability of the CYP1A1-dinotefuran complex over 500 ns. DFT calculations further confirmed the thermodynamic favourability of dinotefuran binding, with serine having a binding energy of -39.68 kcal/mol. This study provides mechanistic insights into the binding behaviour of dinotefuran with CYP1A1 and its potential implications for metabolic disruption and toxicity, providing a foundation for assessing its health risks and environmental impact. Graphical Abstract