Hexaconazole exposure may lead to Parkinson via disrupting glucocerebrosidase and parkin: molecular interaction, dynamics, MMPBSA and DFT based in-silico predictive toxicology

Abstract

Hexaconazole is a known fungicide for agricultural purposes. It has bioaccumulation ability which makes it important for its toxicological characterization. There are various neurological impacts of pollutants on human health. Therefore, in this study, we have done predictive analyses of the interaction mechanism of hexaconazole by molecular interaction analysis, molecular dynamics simulation, and Poisson-Boltzmann surface area (MM-PBSA) to assess hexaconazole's potency to disrupt the homeostasis of glucocerebrosidase (-7.9 kcal/mol) and parkin (-5.67 kcal/mol) proteins which have significant roles in the manifestation of Parkinson disease. The findings reveal that hexaconazole has the potency to form stable interactions with glucocerebrosidase and parkin. This research provides a molecular and atomic-level understanding of how hexaconazole exposure may disrupt the homeostasis of glucocerebrosidase and parkin. The root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration, and hydrogen bonding exhibited the potent molecular interactions of hexaconazole, which may lead to neurological manifestations such as Parkinson disease.

Keywords: agricultural fungicide; computation toxicology; environmental exposure; glucocerebrosidase; hexaconazole; parkin.

Fig. 1

Molecular interaction analyses of β-Glucocerebrosidase with hexaconazole.

Fig. 2

Molecular interaction analyses of parkin with hexaconazole.

Fig. 3

MD simulation analysis of glucocerebrosidase and parkin receptors with Hexaconazole. A) RMSD B) RMSF C) radius of gyration D) hydrogen bond E) SASA Glucocerebrosidase with hexaconazole orange color. Parkin with hexaconazole red color.

Fig. 4

Principal component analysis; A, B) PCA for Glucocerebrosidase with hexaconazole; C, D) PCA for Parkin with hexaconazole.

Fig. 5

A) LUMO position of Hexaconazole B) HOMO position of Hexaconazole; Positive green, negative orange colour.