Structure based High-Throughput Virtual Screening, Molecular Docking and Molecular Dynamics Study of anticancer natural compounds against Fimbriae (FimA) protein of Porphyromonas gingivalis in oral squamous cell carcinoma

Abstract

Abstract Oral cancer is the eighth most common cancer in the world. Tobacco, alcohol, and viruses have been regarded as a well- known risk factors of OCC however, 15% of OSCC cases occurred each year without these known risk factors. Recently a myriad of studies has shown that bacterial infection leads to cancer. Accumulated shreds of evidence demonstrate the role of P. gingivalis in OSCC. The virulence factor FimA of P. gingivalis activated the oncogenic pathways of OSCC by upregulating various cytokines. It also led to the inactivation of a tumor suppressor protein p53 and the activation of the Matrix-metalloproteinase protein 9 (MMP9). The present Insilico study uses High-Throughput Virtual Screening, molecular docking, and molecular dynamics techniques to find the potential compounds against the target protein FimA. The goal of this study is to identify the anti-cancer lead compounds retrieved from natural sources that can be used to develop potent drug molecules to treat P.gingivalis-related OSCC. The anticancer natural compounds library was screened to identify the potential lead compounds. Further, these lead compounds were subjected to precise docking, and based on the docking score potential lead compounds were identified. The top docked receptor-ligand complex was subjected to molecular dynamics simulation. A study of this Insilco finding provides potent lead molecules which help in the development of therapeutic drugs against the target protein FimA in OSCC.