Potential inhibition of Porphyromonas gingivalis Lys-gingipain by 4-caffeoylquinic acid of Moringa oleifera extract: In silico docking and dynamic simulation.

BACKGROUND

Periodontitis is an inflammatory disease of the oral cavity that affects the soft and hard tissues of the periodontium due to dysbiosis by Porphyromonas gingivalis. The bacterium establishes its pathogenicity through its virulence factors, such as fimbriae, and by the releasing proteases like gingipains. The lysine-specific gingipain K (Kgp) is characterized by the presence of a hemagglutinin (HA)-adhesin domain, which provides the micronutrients for the survival of the microbe. 4-Caffeoylquinic acid (4-CQA) is classified as a phenylpropanoid. It exhibits a variety of bioactivities, including anti-inflammatory, antimicrobial, antihistaminic, and antioxidant properties. Moringa oleifera has multiple therapeutic benefits and is used in the treatment of cancer, infections, diabetes, and arthritis. 4-Caffeoylquinic acid was identified among the phenolic phytocomponents present in M. oleifera.

OBJECTIVES

The aim of the present study was to use in silico docking and a dynamic model to evaluate the potential inhibition of Lys-gingipain of P. gingivalis by 4-CQA of M. oleifera.

MATERIAL AND

METHODS

Molecular docking and dynamic simulations of the Lys-gingipain protein and 4-CQA ligands were performed using the Desmond software. The protein structure of Lys-gingipain was downloaded from the Protein Data Bank (PDB) and preprocessed using the optimized potentials for liquid simulations (OPLS 2005) force field.

RESULTS

During the course of the dynamic simulation, the trajectories were saved for the analysis every 100 ns. The stability of the complex was confirmed by a root mean square deviation (RMSD) plot. In the context of molecular docking, the protein (Lys-gingipain) and the ligand (4-CQA) were found to have a potential binding site with the use of hydrogen bonds. The compound had a docking score of -6.6 kcal/mol. According to the results of the dynamic study, as depicted in the RMSD plot, the compound demonstrated stability within the range of 1.0-3.0 Å.

CONCLUSIONS

The inhibition of Lys-gingipain by 4-CQA is a promising avenue for further investigation, whether in vitro or in vivo.