The conformational landscape of RNA translational regulators and their potential as drug discovery targets

dc.contributor.advisorDayie, Theodore Ken_US
dc.contributor.authorLeBlanc, Regan Michaelen_US
dc.contributor.departmentBiochemistryen_US
dc.contributor.publisherDigital Repository at the University of Marylanden_US
dc.contributor.publisherUniversity of Maryland (College Park, Md.)en_US
dc.date.accessioned2016-09-03T05:30:36Z
dc.date.available2016-09-03T05:30:36Z
dc.date.issued2016en_US
dc.description.abstractRNA is an underutilized target for drug discovery. Once thought to be a passive carrier of genetic information, RNA is now known to play a critical role in essentially all aspects of biology including signaling, gene regulation, catalysis, and retroviral infection. It is now well-established that RNA does not exist as a single static structure, but instead populates an ensemble of energetic minima along a free-energy landscape. Knowledge of this structural landscape has become an important goal for understanding its diverse biological functions. In this case, NMR spectroscopy has emerged as an important player in the characterization of RNA structural ensembles, with solution-state techniques accounting for almost half of deposited RNA structures in the PDB, yet the rate of RNA structure publication has been stagnant over the past decade. Several bottlenecks limit the pace of RNA structure determination by NMR: the high cost of isotopic labeling, tedious and ambiguous resonance assignment methods, and a limited database of RNA optimized pulse programs. We have addressed some of these challenges to NMR characterization of RNA structure with applications to various RNA-drug targets. These approaches will increasingly become integral to designing new therapeutics targeting RNA.en_US
dc.identifierhttps://doi.org/10.13016/M2HV2P
dc.identifier.urihttp://hdl.handle.net/1903/18524
dc.language.isoenen_US
dc.subject.pqcontrolledBiochemistryen_US
dc.subject.pquncontrolledAntibioticsen_US
dc.subject.pquncontrolledNuclear Magnetic Resonanceen_US
dc.subject.pquncontrolledRNAen_US
dc.titleThe conformational landscape of RNA translational regulators and their potential as drug discovery targetsen_US
dc.typeDissertationen_US
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