Integrating network toxicology and molecular dynamics simulations to unveil the pathogenic mechanism of benzyl butyl phthalate in atopic dermatitis

This research investigates the molecular mechanisms of benzyl butyl phthalate (BBP) in atopic dermatitis (AD) using network toxicology and molecular dynamics simulation. The environmental toxicity of BBP was systematically predicted and assessed using ADMETlab and ProTox-II. Structural information on BBP was obtained from PubChem, and potential targets were identified using STITCH and CHEMBL. AD-related target genes were retrieved from OMIM and GeneCards. A PPI network was constructed using STRING and Cytoscape to identify key targets. GO and KEGG pathway analyses were conducted to characterize the biological functions and signaling pathways associated with the targets. Molecular docking of BBP with core targets was performed using CB-Dock2. Finally, 100 ns molecular dynamics simulations of BBP-core target complexes were conducted using Gromacs. A total of 119 potential AD-related targets were identified, with six core targets (AKT1, CASP3, KRAS, SRC, EGFR, TNF) highlighted through PPI network analysis. GO and KEGG analyses demonstrated the involvement of these targets in BP, CC, MF, and signaling pathways, with a notable focus on the PI3K-Akt signaling pathway. Molecular docking analysis revealed strong binding affinities between BBP and the core targets, while molecular dynamics simulations confirmed stable interactions between BBP and AKT1, CASP3, and KRAS. This study systematically identifies key targets and molecular mechanisms underlying BBP-induced AD by integrating network toxicology, molecular docking, and molecular dynamics simulations. The findings establish a hierarchical framework linking chemical exposure, molecular interactions, and pathological phenotypes, providing insights into the toxic mechanisms of environmental pollutants from a molecular dynamics perspective.