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A novel therapeutic approach to prevent Helicobacter pylori induced gastric cancer using networking biology, molecular docking, and simulation approaches

Nadeem Khan,Bushra Rehman,T. Almanaa,Salma M. Aljahdali,Yasir Waheed,Asad Ullah,Muhammad Asfandayar,Alhanouf I. Al-Harbi,Tahira Naz,M. Arshad,Samira Sanami,Sajjad Ahmad

Published 2023 in Journal of Biomolecular Structure and Dynamics

ABSTRACT

Abstract Helicobacter pylori infects 50% of the world population and in 80% of cases, the infection progresses to the point where an ulcer develops leading to gastric cancer (GC). This study aimed to prevent GC by predicting Hub genes that are inducing GC. Furthermore, the study objective was to screen inhibitory molecules that block the function of predicted genes through several biophysical approaches. These proteins, such as Mucin 4 (MUC4) and Baculoviral IAP repeat containing 3 (BIRC3), had LogFC values of 2.28 and 3.39, respectively, and were found to be substantially expressed in those who had H. pylori infection. The MUC4 and BIRC3 inhibit apoptosis of infected cells and promote cancerous cell survival. The proteins were examined for their Physico-chemical characteristics, 3D structure and secondary structure analysis, solvent assessable surface area (SASA), active site identification, and network analysis. The MUC4 and BIRC3 expression was inhibited by docking eighty different compounds collected from the ZINC database. Fifty-seven compounds were successfully docked into the active site resulting in the lowest binding energy scores. The ZINC585267910 and ZINC585268691 compounds showed the lowest binding energy of −8.5 kcal/mol for MUC4 and −7.1 kcal/mol for BIRC3, respectively, and were considered best-docked solutions for molecular dynamics simulations. The mean root mean square deviation (RMSD) value for the ZINC585267910-MUC4 complex was 0.86 Å and the ZINC585268691-BIRC3 complex was 1.01 Å. The net MM/GBSA energy value of the ZINC585267910-MUC4 complex estimated was −46.84 kcal/mol and that of the ZINC585268691-BIRC3 complex was −44.84 kcal/mol. In a nutshell, the compounds might be investigated further as an inhibitor of the said proteins to stop the progress of GC induced by H. pylori. Communicated by Ramaswamy H. Sarma

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