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. 2022 Apr 25;27(9):2749.
doi: 10.3390/molecules27092749.

Gene Interaction Network Analysis Reveals IFI44L as a Drug Target in Rheumatoid Arthritis and Periodontitis

Pradeep Kumar Yadalam  1 , Thilagar Sivasankari  2 , Santhiya Rengaraj  2 , Maryam H Mugri  3 , Mohammed Sayed  4 , Samar Saeed Khan  5 , Mona Awad Kamil  6 , Shilpa Bhandi  7 , A Thirumal Raj  8 , Shankargouda Patil  5 , Artak Heboyan  9
Affiliations

Gene Interaction Network Analysis Reveals IFI44L as a Drug Target in Rheumatoid Arthritis and Periodontitis

Pradeep Kumar Yadalam et al. Molecules. .

Abstract

Objective: Despite extensive research on periodontitis and rheumatoid arthritis, the underlying molecular connectivity between these condition remains largely unknown. This research aimed to integrate periodontitis and rheumatoid arthritis gene expression profiles to identify interconnecting genes and focus to develop a common lead molecule against these inflammatory conditions.

Materials and methods: Differentially expressed genes (DEGs) of periodontitis and rheumatoid arthritis were identified from the datasets retrieved from the Gene Expression Omnibus database. The network was constructed by merging DEGs, and the interconnecting genes were identified and ranked using GeneMANIA. For the selected top ranked gene, the potential inhibitor was searched using FINDSITEcomb2.0. Subsequently, the molecular docking and molecular dynamics were performed to determine the binding efficiency and protein-ligand complex stability, respectively.

Results: From the network analysis, IFN-induced protein 44-like (IFI44L) was identified as a top ranked gene involved in most of the immunological pathway. With further virtual screening of 6507 molecules, vemurafenib was identified to be the best fit against the IFI44L target. The binding energy and stability of IFI44L with vemurafenib were investigated using molecular docking and molecular dynamics simulation. Docking results show binding energy of -7.7 Kcal/mol, and the simulation results show stability till 100 ns.

Conclusions: The identified IFI44L may represent a common drug target for periodontitis and rheumatoid arthritis. Vemurafenib could be a potent anti-inflammatory drug for both diseases.

Keywords: drug target; molecular docking; periodontitis; rheumatoid arthritis; vemurafenib.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Integrated network of periodontitis and rheumatoid arthritis.
Figure 2
Figure 2
Binding interaction of vemurafenib with IFI144L.
Figure 3
Figure 3
Root mean square deviation (RMSD) of the protein–ligand complex.
Figure 4
Figure 4
Root mean square fluctuation (RMSF) plot.
Figure 5
Figure 5
Bar chart displaying the aminoacid contributing to the ligand interaction.
See this image and copyright information in PMC

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References

    1. Ong G. Periodontal reasons for tooth loss in an Asian population. J. Clin. Periodontol. 1996;23:307–309. doi: 10.1111/j.1600-051X.1996.tb00550.x. - DOI - PubMed
    1. Nilsson H., Berglund J.S., Renvert S. Periodontitis, tooth loss and cognitive functions among older adults. Clin. Oral Investig. 2018;22:2103–2109. doi: 10.1007/s00784-017-2307-8. - DOI - PubMed
    1. Larsson L. Current Concepts of Epigenetics and Its Role in Periodontitis. Curr. Oral Health Rep. 2017;4:286–293. doi: 10.1007/s40496-017-0156-9. - DOI - PMC - PubMed
    1. Pan W., Wang Q., Chen Q. The cytokine network involved in the host immune response to periodontitis. Int. J. Oral Sci. 2019;11:30. doi: 10.1038/s41368-019-0064-z. - DOI - PMC - PubMed
    1. Hart T.C. Genetic considerations of risk in human periodontal disease. Curr. Opin. Periodontol. 1994;1994:3–11. - PubMed

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