Targeting MurB from Helicobacter pylori: insights from virtual screening, molecular docking and molecular dynamics simulation

• Published in: Molecular simulation Vol. 50; no. 5; pp. 379 - 393
• Main Authors: Sharma, Abhishek, Singh, Amit Kumar, Muthukumaran, Jayaraman, Jain, Monika
• Format: Journal Article
• Language: English
• Published: Abingdon Taylor & Francis 23.03.2024; Taylor & Francis Ltd
• Subjects: Bacteria; Biosynthesis; Enzymes; Helicobacter pylori; Inhibitors; MM/PBSA; Molecular docking; Molecular dynamics; molecular dynamics simulation; MurB; Proteins; Reductases
• ISSN: 0892-7022; 1029-0435
• DOI: 10.1080/08927022.2024.2316818

Helicobacter pylori is a gram-negative, helical-shaped bacteria found in the mucus lining of the stomach of humans responsible for causing sores or an ulcer. H. pylori is becoming a multi-drug resistant bacterium, which in turn demands the need for development of alternative treatment strategies for the proper management of diseases. The peptidoglycan biosynthesis pathway is critical for the synthesis of cell walls and for the survival of H. pylori. There are several crucial enzymes in this biosynthesis pathway which can act as significant drug targets against H. pylori. One of these important enzymes is UDP-N-acetylenolpyruvoylglucosamine reductase (MurB), which catalyses an important committed step of cell wall biosynthesis. In the present study, we performed a high throughput virtual screening using the Enamine HTSC library against the MurB enzyme. The molecules were also screened for druglike properties by ADME screening, toxicity, and tumorigenic nature, followed by MD simulations. We found that Z102621114_1 and Z228235240_1 ligand molecules can act as potential inhibitors of MurB protein. Our results suggest, these molecules may be able to meet the demand for novel antimicrobials to treat H. pylori medication resistance. The subsequent experimental investigations can increase their potential as a novel agents against H. pylori infections. Research highlights Helicobacter pylori infects 50% of the Global population. Helicobacter pylori infection is associated with gastric cancer. MurB is a key drug target protein as it is responsible for cell wall synthesis. Z102621114_1 and Z228235240_1 were identified as potential inhibitors of MurB of Helicobacter pylori.