Unveiling HuB genes and drug design against Helicobacter pylori infection by network biology and biophysics techniques

Abstract

Helicobacter pylori (H. pylori) is mainly considered for causing chronic gastritis, which can lead to several secondary complications like peptic ulcer and pre-malignant lesions for example atrophic gastritis, intestinal dysplasia and metaplasia, with the etiological factor of developing gastric cancer. Recent research demonstrates that H.pylori colonizes the stomach mucosa of more than fifty populations around the globe. This research focuses on unveiling hub genes, and diagnostic and drug targets against said organism by utilizing various types of networking biology and biophysical approaches. In data retrieval, the GSE19826 dataset was obtained from the gene expression omnibus database and microarray data set from array express. Geo2r analysis predicted a total number of 7 DEGs and 10 hub genes, next functional protein association network analysis (STRING) unveiled that among 10 Hub genes only 3 genes were found more interactive with other genes and involved in pathogenesis, The shortlisted three genes were further analyzed for survival analysis using Gene Expression Profiling Interactive Analysis (GEPIA) and predicted the survival rate of targeted genes. Moreover, functional enchainment analysis was done using the ToppFun server, the server predicted that COL11A1 and COL10A1 were more involved in the pathogenesis of the H. pylori infection. Furthermore, the COL10A1 gene was subjected to protein structure prediction. In molecular docking analysis, the asinex antibacterial library was screened for potential inhibitors, and one compound was predicted as a strong inhibitor with the best binding at −10.23 kcal/mol. The docking results were further validated through molecular dynamic simulation analysis and the MD simulation analysis evaluated the dynamic movement of the docked complex in various nanoseconds, the MD simulation results predicted that the docked complexes are stable throughout the simulation and can be used as a potential inhibitor against the said pathogen, however experimental study is required to further validate the predicted results and design drug against targeted pathogen.