What question did this study set out to answer?

This study aims to explore the therapeutic mechanisms of Camellia sinensis phytochemicals in treating periodontitis through molecular modeling.

May 16, 2026Open Access

Integrative Multi-Scale Molecular Modeling Reveals Novel Therapeutic Mechanisms of Camellia sinensis in Periodontitis

Key Points

This study aims to explore the therapeutic mechanisms of Camellia sinensis phytochemicals in treating periodontitis through molecular modeling.
Utilized an integrated in silico strategy combining network pharmacology and molecular docking assessment.
Conducted molecular dynamics (MD) simulations over 100 ns to analyze binding stability.
Identified 23 overlapping targets and evaluated central hubs such as MPO and AKT1.
MPO was identified as the most favorable core target with a binding affinity of −9.63 kcal/mol for (−)-gallocatechin gallate.
MM/PBSA calculations showed binding energies of (−)-gallocatechin gallate and gallocatechin 3-O-gallate of −27.66 ± 7.53 kcal/mol and −26.09 ± 8.96 kcal/mol, respectively.
Gallate-containing catechins demonstrated stable interactions with a notable binding advantage over standard inhibitors.

Abstract

Objectives: This study aimed to elucidate the multi-target therapeutic mechanisms of Camellia sinensis phytochemicals in periodontitis using an integrative multi-scale molecular modeling strategy. Methods: An integrated in silico strategy was employed, incorporating network-based pharmacological analysis, protein interaction network evaluation, molecular docking assessment, density functional theory (DFT) computations, molecular dynamics (MD) trajectory analysis, MM/PBSA-derived binding energy estimation, and residue-level energetic contribution profiling. Overlapping targets between C. sinensis and periodontitis-associated genes were identified, followed by topological screening to determine crucial hub proteins. The most promising target was subjected to detailed structural and energetic evaluation. Results: Intersection analysis identified 23 common targets, with AKT1, myeloperoxidase (MPO), MMP2, MMP3, MMP9, STAT1, IL2, BCL2, ESR1, and SERPINE1 emerging as central hubs. Functional enrichment highlighted AGE–RAGE and JAK–STAT signaling pathways and extracellular matrix remodeling processes. Docking revealed MPO as the most favorable core target. Gallate-containing catechins, particularly (−)-gallocatechin gallate (−9.63 kcal/mol) and gallocatechin 3-O-gallate (−9.52 kcal/mol), exhibited more favorable binding affinities than the standard inhibitor 4-ABAH (−6.02 kcal/mol). DFT analysis demonstrated moderate HOMO–LUMO gaps (4.31–4.78 eV) and favorable dipole moments supporting electronic stability and reactivity. MD simulations confirmed stable complex formation over 100 ns, with persistent hydrogen bonding and consistent ligand retention. MM/PBSA calculations further validated a favorable binding of (−)-gallocatechin gallate (−27.66 ± 7.53 kcal/mol) and gallocatechin 3-O-gallate (−26.09 ± 8.96 kcal/mol), comparable to or exceeding 4-ABAH (−25.88 ± 4.44 kcal/mol). Conclusions: C. sinensis phytochemicals, particularly gallate-containing catechins, exhibit stable, energetically favorable interactions with MPO, supporting their potential as competitive inhibitors that modulate oxidative stress and inflammatory pathways in periodontitis.

Integrative Multi-Scale Molecular Modeling Reveals Novel Therapeutic Mechanisms of Camellia sinensis in Periodontitis

Key Points

Abstract

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