Environmentally friendly strategy for discovering the toxicity and mechanisms of nerve injury induced by acrylamide via network toxicology combined with molecular dynamics simulation

This study aimed to explore an efficient and low-cost toxicological analysis method for environmental pollutants by taking the mechanism of acrylamide induced nerve injury as an example. Potential targets of acrylamide were retrieved by combining the ChEMBL, Super-PRED, SwissTargetPrediction, Similarity ensemble approach, and STITCH databases. The GeneCards and OMIM databases were searched to identify the potential gene pool related to neurotoxicity and to identify intersecting genes. These genes were subsequently entered into the STRING database to construct a protein interaction network. GO and KEGG analyses were conducted by using the DAVID platform, and the molecular docking of intersection targets was assessed by using AutoDock 1.5.7 software. Finally, molecular dynamics simulation was used to verify the stability of the optimal binding model for molecular docking. After screening, 142 intersection targets were obtained, with TP53, PIK3CA, PIK3R1, PTK2, and GRB2 being the key targets of acrylamide-induced nerve injury. GO and KEGG enrichment analyses results showed that the mechanism of action is related mainly to the PI3K-Akt signaling pathway and microRNAs involved in cancer pathogenesis. Molecular docking confirmed that acrylamide was strongly bound to key targets. The stability of the interaction between acrylamide and TP53 was verified by molecular dynamics simulation. The proposed strategy not only reduces the initial experimental cost of identifying new pollutants and increases the amount of information on the toxic effects of environmental pollutants but also improves the efficiency of regulatory authorities in identifying environmental pollutant hazards.