No 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 nd 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 identi ed. The top docked receptor-ligand complex was subjected to molecular dynamics simulation. A study of this Insilco nding provides potent lead molecules which help in the development of therapeutic drugs against the target protein FimA in OSCC.

Nucleoside diphosphate kinase (NDK) protein of Porphyromonas gingivalis (P. gingivalis) plays an important role in immune evasion and apoptosis inhibition of host cells. It has the potential to cause cancer, however, its structure has not yet been determined. Here we established a 3D structure of P.gingivalis NDK protein using an in-silico approach and performed the structural analysis of the model protein. 3D structure of NDK was predicted through homology modelling using modeller. Structural domains predicted for the model belongs to the NDK family. Structural homology was further confirmed by functional annotation of the model which includes ATP binding and nucleotide diphosphate kinase function, indicating that it is an NDK protein. Structural alignment of the putative model shows the alpha-beta folds are structurally conserved among NDK from prokaryotes and eukaryotes. The structure-based phylogenetic analysis depicts a significant evolutionary relationship of the modeled protein with the NDK of prokaryotes. Furthermore, the MD simulation approach stabilized the model structure and provides a thermo-stable protein structure that can be used as a therapeutic target for further studies.

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.

The Nucleoside diphosphate kinase (NDK) protein of Porphyromonas gingivalis (P. gingivalis) plays a crucial role in immune evasion and inhibition of apoptosis in host cells and has the potential to cause cancer. However, its structure has not yet been characterized. We used an in-silico approach to determine the 3D structure of the P. gingivalis NDK. Furthermore, structural characterization and functional annotation were performed using computational approaches. The 3D structure of NDK was predicted through homology modeling. The structural domains predicted for the model protein belong to the NDK family. Structural alignment of prokaryotic and eukaryotic NDKs with the model protein revealed the conservation of the domain region. Structure-based phylogenetic analysis depicted a significant evolutionary relationship between the model protein and the prokaryotic NDK. Functional annotation of the model confirmed structural homology, exhibiting similar enzymatic functions as NDK, including ATP binding and nucleoside diphosphate kinase activity. Furthermore, molecular dynamic (MD) simulation technique stabilized the model structure and provides a thermo-stable protein structure that can be used as a therapeutic target for further studies.