Ph. D. Thesis Colloquium
Name: Mr. Dibyendu Mondal
Research Supervisor: Prof. Govardhan Reddy
Title: RNA Structural Plasticity and Conformational Dynamics in Regulation of Biological Function
Date and Time: Tuesday, 14th July at 11:00 a.m.
Venue: Rajarshi Bhattacharyya Memorial Lecture Hall, Chemical Sciences Building
Abstract:
Precise regulation of biological processes is essential for survival, adaptation, and stress response in all life forms. While eukaryotes have evolved highly complex regulatory networks involving proteins, metabolites, and compartmentalized signalling pathways, bacteria and viruses often rely on compact RNA-based mechanisms to monitor their environment and control gene expression. Structured regulatory RNAs, including riboswitches and genomic RNA elements, exploit intrinsic structural plasticity to sense diverse molecular cues and convert recognition events into functional outcomes1,2. This thesis investigates how RNA conformational dynamics and ionic environments shape regulatory mechanisms in bacterial and viral systems.
A central challenge in RNA biology is that many regulatory processes involve transient, heterogeneous, and ion-sensitive conformational states that are difficult to resolve using state-of-the-art experimental techniques. My work complements the experiments by employing computer simulations of RNA models to investigate RNA regulatory processes by computing their conformational landscapes, and the role of metal ions and cognate ligands in modulating the landscape3,4.
The thesis addresses the important question of how RNA achieves selective recognition and regulatory control despite its flexible, highly charged, and dynamic nature. Riboswitches provide a powerful framework to address this question because they sense a wide spectrum of signals, from metabolites and charged ligands to RNA partners, and transmit this information through structural rearrangements that alter gene expression5,6. By comparing regulatory RNAs that respond to chemically and electrostatically distinct inputs, this work investigated how local recognition events are coupled to global conformational changes and how ionic environments tune these processes. Interestingly, the same principles extend to viral genomic RNA, where self-recognition and assembly require coordinated structural transitions and ion-mediated stabilization2,7. Together, these studies show that RNA regulation emerges from dynamic conformational ensembles, highlighting structural plasticity and electrostatic control as general mechanisms underlying microbial gene regulation and viral RNA function.
References:
(1) Kavita, K.; Breaker, R. R. Discovering Riboswitches: The Past and the Future. Trends Biochem. Sci. 2023, 48 (2), 119–141. https://doi.org/10.1016/j.tibs.2022.08.009.
(2) Dubois, N.; Marquet, R.; Paillart, J.-C.; Bernacchi, S. Retroviral RNA Dimerization: From Structure to Functions. Front. Microbiol. 2018, 9. https://doi.org/10.3389/fmicb.2018.00527.
(3) Denesyuk, N. A.; Thirumalai, D. How Do Metal Ions Direct Ribozyme Folding? Nat. Chem. 2015, 7 (10), 793–801. https://doi.org/10.1038/nchem.2330.
(4) Denesyuk, N. A.; Thirumalai, D. Coarse-Grained Model for Predicting RNA Folding Thermodynamics. J. Phys. Chem. B 2013, 117 (17), 4901–4911. https://doi.org/10.1021/jp401087x.
(5) Mondal, D.; Reddy, G. Conformational Pathways of Translational T-Box Riboswitch Governing TRNA Recognition for Gene Regulation. J. Phys. Chem. Lett. 2025, 16, 10009–10019. https://doi.org/10.1021/acs.jpclett.5c02341.
(6) Mondal, D.; Habibullah, S.; Baidya, L.; Singh Harariya, M.; Reddy, G. Transition Metal Binding Drives Folding of a Metalloregulatory Riboswitch by Modulating Conformational Flexibility at Helical Junctions. J. Chem. Theory Comput. 2025, 21 (23), 12328–12341. https://doi.org/10.1021/acs.jctc.5c01338.
(7) Mondal, D.; Habibullah, S.; Reddy, G. Dimerization Mechanism of HIV-1 RNA Hairpins to Extended Duplex Structures. J. Phys. Chem. B 2026, 130 (7), 2109–2117. https://doi.org/10.1021/acs.jpcb.5c07936.