Life Sciences & Biotechnology
Title : | Modelling Co-transcriptional Folding of Riboswitches |
Area of research : | Life Sciences & Biotechnology |
Focus area : | Transcriptional Regulation |
Principal Investigator : | Dr. Govardhan Reddy Patluri, Indian Institute Of Science, Bangalore, Karnataka |
Timeline Start Year : | 2024 |
Timeline End Year : | 2027 |
Contact info : | greddy.p@gmail.com |
Details
Executive Summary : | Riboswitches are non-coding RNA that regulate gene expression in bacteria, consisting of an aptamer domain (AD) and an expression platform (EP). They change their structure in response to ligand binding, causing structural changes in AD and EP signaling gene regulation. Riboswitches are crucial for bacteria's survival and have become targets for discovering new antibacterial drugs. Their ability to bind to specific ligands and change structure is exploited in the design of metal ion sensors and Boolean logic gates. This proposal aims to provide fundamental insights into the mechanisms related to riboswitches' structural changes using computer simulations. A multiscale modeling strategy will be adopted to probe structural changes at multiple length scales, while atomistic RNA models will be used to probe local secondary structural changes at the atomistic level. The study will focus on the co-transcriptional folding of riboswitches to probe AD conformations populated as a function of transcript length and the effect of the ligand on these conformations. The proposed study will reveal the interplay between the folded AD and EP folding as it is synthesized. The mechanism of structural transition in the riboswitch upon ligand binding is not completely clear, but the study will focus on the full riboswitch upon ligand binding. Understanding intermediate structures can help design new molecules that can potently bind to these intermediates and prevent the structural transition, acting as antibacterial drugs. |
Total Budget (INR): | 46,81,380 |
Organizations involved