Computational perspectives on Chlorpyrifos and its degradants as human glutathione S-transferases inhibitors: DFT calculations, molecular docking study and MD simulations

Chlorpyrifos is the toxicant chemical from the class of organophosphorus insecticides. The insecticide undergoes environmental degradation to chlorpyrifos‐oxon (CPYO), des‐ethyl chlorpyrifos (DEC), 3,5,6‐trichloro‐2‐methoxypyridine (TMP) and 3,5,6‐trichloro‐2‐pyridinol (TCP). Herein, CPF along with its degradants were optimized employing density functional theory (DFT) and B3LYP/6-311G+(d,p) basis set to elucidate their thermal and frontier molecular orbital properties. The DFT outcome revealed that TCP showed the lowest HOMO-LUMO gap (4.38 eV), also highest dipole moment, electrophilicity index and basicity. Docking was done using AutoDock 4.2.6 against human glutathione S-transferases to search binding affinity and interactions of all pollutants with the protein. The docking results expressed that TCP required least binding energy (−5.51 kcal mol⁻¹) which is relatable to the DFT studies and might act as the most powerful inhibitor. GROMACS 5.1.1 was utilized to perform simulation studies for each ligand–protein docked complexes. Results concluded that CPF, DEC, TMP, CPYO and TCP could possibly perform as toxic and inhibit enzymatic activity by interrupting the metabolic pathways in humans.