In Silico Interaction of Phellilane L with HmuY: A Promising Therapeutic Strategy against Porphyromonas gingivalis in Chronic Periodontitis.

Abstract

This study investigates the in silico interaction between Phellilane L, a sesquiterpene metabolite from Phellinus linteus, and the Porphiromonas gingivalis HmuY protein, a key player in chronic periodontitis pathogenesis. The goal is to assess the potential of Phellilane L as a therapeutic agent against periodontal infections. Molecular docking and dynamics simulations were used to explore the interaction between Phellilane L and HmuY. Lipinski's rule of five, Wiener index, and MM/GBSA calculations were performed to assess drug-likeness, molecular connectivity, and binding affinity. Python 2.7, AutoDock 4.2, and Flare software were used to perform docking, energy calculations, and molecular dynamics simulations. Phellilane L showed favorable drug-likeness, adhering to Lipinski's rule of five. The Wiener index of 493 indicates simplicity in molecular structure, beneficial for drug absorption. Docking results revealed key interactions with HmuY, with binding energy of -7.45 μM and stable van der Waals and hydrogen bond interactions. MM/GBSA analysis indicated a favorable binding free energy of -27.45 kcal/mol, with significant contributions from van der Waals and electrostatic interactions. Phellilane L demonstrates strong binding affinity to HmuY, potentially inhibiting heme acquisition, essential for P. gingivalis survival. These findings suggest Phellilane L as a promising candidate for developing novel therapeutic approaches for treating periodontal disease.