Computational Exploration and Molecular Docking Analysis of Mycobacterium Tuberculosis RpfB Protein

Abstract

The RpfB protein, a vital component of bacterial cell wall metabolism, is particularly significant in the context of Mycobacterium tuberculosis, the causative agent of tuberculosis. Within this pathogen, RpfB plays a pivotal role in cell growth, division, and virulence, contributing to the survival and persistence of M. tuberculosis within the host. As a member of the Resuscitation-Promoting Factor (Rpf) family, RpfB is crucial for reactivating dormant cells, a process essential for M. tuberculosis to establish latent infections and evade host immune responses. Through its enzymatic activity, RpfB facilitates peptidoglycan remodeling and cell wall synthesis in M. tuberculosis, influencing bacterial physiology and pathogenicity. Elucidating the molecular mechanisms by which RpfB operates in M. tuberculosis not only enhances our understanding of bacterial persistence but also unveils potential targets for novel antimicrobial interventions against tuberculosis, a global health threat of immense significance. The vulnerability of Mycobacterium tuberculosis to various drugs and its persistence has stood as a hurdle in the race against eradication of the pathogenicity of the bacteria. Identification of novel antituberculosis compounds is highly demanding as the available drugs are resistant. The ability of the bacteria to surpass the body's defenses and adapt itself to survive for disease reactivation is contributed by secreted proteins called resuscitating promoting factors (Rpfs). These factors aid in virulence and resuscitation from dormancy of the bacteria. Sequence analysis of RpfB was performed and compounds were first screened for toxicity and high-throughput virtual screening eliminating the toxic compounds. To understand the mechanism of ligand binding and interaction, molecular docking was performed for the compounds passing through the filter resulting with better docking studies predicting the possible binding mode of the inhibitors to the protein.