Research on the influence of bisphenol A on precocious puberty based on network toxicology and molecular dynamics simulation.

PURPOSE: Precocious puberty (PP) is a pediatric endocrine disorder. Bisphenol A (BPA) is an endocrine disruptor. This study aimed to computationally investigate BPA-associated PP targets and mechanisms via network toxicology and molecular dynamics.

METHODS

BPA information was obtained from PubChem. Target genes were collected from multiple databases, and PP-related genes were identified via GeneCards and Online Mendelian Inheritance in Man. ProTox was used to predict BPA toxicity. After gene set intersection, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed (P < 0.05). A protein-protein interaction (PPI) network was constructed to identify key genes, and a BPA-key gene-pathway network was established. The subcellular localization of key genes was analyzed, followed by molecular docking (score ≤ -5 kcal/mol) and 100-ns GROMACS-based molecular dynamics simulation.

RESULTS

A total of 722 BPA targets and 1,126 potential PP targets were identified using multiple databases. Their intersection gave 99 potential target genes for BPA-induced PP, and further intersection with 16 toxic target genes of BPA resulted in six candidate genes. GO enrichment had 378 pathways, and KEGG enrichment had 18 pathways, with the top 10 being related to processes such as chemical carcinogenesis-receptor activation. The PPI network analysis revealed four key genes. Subcellular localization showed key gene product distribution. Molecular docking revealed a strong binding force, and molecular dynamics simulation further indicated that the complexes formed by BPA and these proteins were structurally stable.

CONCLUSIONS

This study identified potential BPA-PP targets, providing a hypothesis-generating basis for future validation.