Exploring the toxicological effects of DOTP exposure on periodontitis by combining molecular docking and molecular dynamics simulations.

This research delved into the molecular mechanism underlying dioctyl terephthalate (DOTP)-related periodontitis (PD) through the application of network toxicology, molecular docking, and molecular dynamics simulations. By leveraging data from SwissTargetPrediction, SuperPred, and GeneCards databases, targets associated with DOTP toxicity and PD were pinpointed, leading to the identification of 37 shared targets through a comprehensive analysis. Enrichment analysis unveiled significant implications in inflammatory responses (e.g., the AGE-RAGE signaling pathway) and immune regulatory pathways (e.g., the C-type lectin receptor pathway). Core targets (PTGS2, MAPK14, NFKB1, STAT1) were pinpointed utilizing Cytoscape and molecular docking techniques. DOTP exhibited robust binding to these targets through hydrogen bonding and hydrophobic interactions, with the DOTP-PTGS2 complex displaying the most favorable binding energy (- 7.1 kcal/mol). Molecular dynamics simulations validated the stability of this complex, demonstrating the lowest root mean square deviation (RMSD) of 0.22 nm and the largest buried solvent-accessible surface area (Buried SASA) of 12 nm, indicating its superior stability. This investigation elucidates the molecular basis of DOTP-related PD, underscores the efficacy of network toxicology and computational modeling in environmental health risk assessment, and provides a theoretical framework for targeted interventions.