Periodontal Implications of Porphyromonas gingivalis-Derived Metabolites in Host Antioxidant and Anti-Inflammatory Mechanisms: A Computational Analysis.

BACKGROUND Metabolites of Porphyromonas gingivalis (P. gingivalis), a key periodontal pathogen, can interfere with host antioxidant and anti-inflammatory mechanisms. Paraoxonase 1 (PON1) is an enzyme that counteracts oxidative damage and inflammation. Understanding the interaction between P. gingivalis-derived metabolites and PON1 could provide insights into disease progression and therapeutic targets. This study investigated PON1 expression in oral tissues and evaluated the potential inhibitory effects of P. gingivalis-derived metabolites on PON1 function using computational approaches. MATERIAL AND METHODS PON1 expression in oral tissues was analyzed using GeneCards, and its protein interaction networks were examined via the STRING database. The crystal structure of PON1 (PDB ID: 1V04) was optimized for molecular docking. A curated set of P. gingivalis metabolites was retrieved from the Virtual Metabolic Human (VMH) database and filtered based on molecular weight and host interaction potential. Molecular docking was performed using Schrödinger's Glide module, and molecular dynamics (MD) simulations were conducted over 100 ns with GROMACS using the AMBER99SB force field to evaluate PON1-metabolite stability. RESULTS PON1 was highly expressed in the oral epithelium and salivary glands, forming key interaction networks involved in oxidative stress and inflammation. Screening of 1276 P. gingivalis metabolites identified C₃₈H₇₀O₁₀P⁺ as a high-affinity binder to PON1 (-9.784 kcal/mol). MD simulations showed that this metabolite induced conformational changes in PON1, potentially impairing its antioxidant and anti-inflammatory functions. CONCLUSIONS These findings suggest that P. gingivalis-derived metabolites contribute to periodontitis and its systemic complications by disrupting PON1-mediated host defense mechanisms.