Ph.D. THESIS COLLOQUIUM
Presenter Name: Sunil Kumar
Ph.D Supervisor: Prof. Govardhan P. Reddy
Date & Time: 25 July, 2022, Monday at 4:00 pm through MICROSOFT TEAMS
Title: Metal Ion Mediated Riboswitch Folding and Cognate Ligand Sensing
Riboswitches are noncoding RNA molecules that can control gene expression upon cognate ligand binding . Riboswitches are primarily present in bacteria and are crucial for bacteria’s survival, which makes riboswitches attractive targets for discovering new antimicrobials . Designing drugs that target a riboswitch function can be accelerated by understanding the effect of physicochemical factors (like ions, temperature, pressure, cosolvents, and pH) on the riboswitch folding and cognate ligand binding. The magnesium (Mg2+) ions possess the unique capability to exhibit site-specific binding along the RNA chain and modulate the population of functionally relevant RNA tertiary structures [3-5]. In this thesis, I will discuss the effect of Mg2+ on the folding thermodynamics and kinetics of the riboswitches and how cations assist riboswitches in attaining specific tertiary structures . I will also provide insight into how the anionic cognate ligands bind to the polyanionic RNA backbone. Further, I will discuss the properties that contribute to cations’ binding in specific riboswitch sites. Finally, I will discuss how riboswitch responds to the cognate ligand binding and transmits the ligand binding information to the gene expression machinery.
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 Kumar, S.; Reddy, G. TPP riboswitch populates holo-form-like structure even in the absence of cognate ligand at high Mg2+ concentration. J. Phys. Chem. B 2022, 126, 2369–2381.
 Halder, A.; Kumar, S.; Valsson, O.; Reddy, G. Mg2+ sensing by an RNA fragment: Role of Mg2+ -coordinated water molecules. J. Chem. Theory Comput. 2020, 16, 6702–6715