@article {153398, title = {Computational analysis of the effect of a binding protein (RbpA) on the dynamics of Mycobacterium tuberculosis RNA polymerase assembly.}, journal = {PLoS One}, volume = {20}, year = {2025}, month = {2025}, pages = {e0317187}, abstract = {

BACKGROUND: RNA polymerase-binding protein A (RbpA) is an actinomycetes-specific protein crucial for the growth and survival of the pathogen Mycobacterium tuberculosis. Its role is essential and influences the transcription and antibiotic responses. However, the regulatory mechanisms underlying RbpA-mediated transcription remain unknown. In this study, we employed various computational techniques to investigate the role of RbpA in the formation and dynamics of the RNA polymerase complex.

RESULTS: Our analysis reveals significant structural rearrangements in RNA polymerase happen upon interaction with RbpA. Hotspot residues, crucial amino acids in the RbpA-mediated transcriptional regulation, were identified through our examination. The study elucidates the dynamic behavior within the complex, providing insights into the flexibility and functional dynamics of the RbpA-RNA polymerase interaction. Notably, potential allosteric mechanisms, involving the interface of subunits α1 and α2 were uncovered, shedding light on how RbpA modulates transcriptional activity.

CONCLUSIONS: Finally, potential ligands meant for the α1-α2 binding site were identified through virtual screening. The outcomes of our computational study serve as a foundation for experimental investigations into inhibitors targeting the RbpA-regulated dynamics in RNA polymerase. Overall, this research contributes valuable information for understanding the intricate regulatory networks of RbpA in the context of transcription and suggests potential avenues for the development of RbpA-targeted therapeutics.

}, keywords = {Bacterial Proteins, Binding Sites, DNA-Directed RNA Polymerases, Molecular Dynamics Simulation, Mycobacterium tuberculosis, Protein Binding, Transcription, Genetic}, issn = {1932-6203}, doi = {10.1371/journal.pone.0317187}, url = {https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0317187}, author = {Bheemireddy, Sneha and Sowdhamini, Ramanathan and Srinivasan, Narayanaswamy} }