Please use this identifier to cite or link to this item: http://dr.iiserpune.ac.in:8080/xmlui/handle/123456789/6834
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dc.contributor.advisorCHUGH, JEETENDERen_US
dc.contributor.authorTARANG, GUNEET SINGHen_US
dc.date.accessioned2022-05-11T05:26:32Z-
dc.date.available2022-05-11T05:26:32Z-
dc.date.issued2022-04-
dc.identifier.citation52en_US
dc.identifier.urihttp://dr.iiserpune.ac.in:8080/xmlui/handle/123456789/6834-
dc.description.abstractDouble-stranded RNA-binding domains (dsRBDs) target topologically distinct dsRNAs in a variety of biological pathways that are central to viral replication, cancer causation, neurodegeneration, etc. TRBP is one of the proteins in the RNA interference pathway known to interact with a large number of the precursor miRNAs, in a non-sequence specific manner, during their maturation phase. Our group has recently shown that TRBP targets topologically distinct dsRNAs (due to internal loops and bulges) in a unique fashion, and conformational dynamics in TRBP are pivotal for such substrate promiscuity. To further the understanding of the adaptive targeting by TRBP, this study aims to perturb the conformational adaptability of the protein by designing intelligent mutations at critical residues showing dynamics that is crucial for dsRNA targeting. Using atomistic MD simulations, the effect of introducing these mutations is seen to propagate throughout the dsRBD in the form of increased rigidity and perturbed distances between RNA-binding regions. Based on previous literature and current results, the role of different RNA-binding regions in discriminating between potential dsRNA substrates has been explored. To validate the results obtained in simulations, mutant dsRBD clones have been generated, and the purification of the expressed protein has been attempted. Follow-up dynamics-oriented experimental work based on these results would help establish principles of dsRBD-dsRNA interaction and be an excellent case study in dynamics-based protein design.en_US
dc.language.isoen_USen_US
dc.subjectMD Simulationsen_US
dc.subjectdsRNAen_US
dc.subjectTAR RNA Binding Proteinen_US
dc.subjectTRBPen_US
dc.subjectdsRNA binding proteinen_US
dc.subjectRNA interferenceen_US
dc.subjectmiRNAen_US
dc.subjectprotein conformational dynamicsen_US
dc.subjectdisulfide engineeringen_US
dc.subjectallosteryen_US
dc.titleMutational perturbation to the intrinsic adaptability of a dsRBD: implications to RNA shape-dependent targetingen_US
dc.typeThesisen_US
dc.type.degreeBS-MSen_US
dc.contributor.departmentDept. of Biologyen_US
dc.contributor.registration20171057en_US
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