Giambasu, George M˘ad˘alin2011-10-132011-10-132010-08https://hdl.handle.net/11299/116673University of Minnesota Ph.D. dissertation. August 2010. Major: Chemistry. Advisor: Darrin M. York. 1 computer file (PDF); viii, 104 pages.RNA possess a diverse ensemble of conformations that interchange on time scales that range from femtoseconds to milliseconds. This conformational variability has a profound effect on RNA function, and has been exploited in RNA molecules such as aptamers, aptazymes, and riboswitches that have been engineered to be allosterically controlled. Central to this work is the questions of how RNA conformational variability affects with its catalytic activity. We employ a set of diverse theoretical and simulation tools, such as molecular dynamics, free energy calculations, and path sampling that greatly extend the capability of structural and molecular biology experiments to reveal atomic level details of RNA energetics and dynamics. Our systems of interest are two prototypical catalytic RNA systems: L1 ligase and Hammerhead ribozymes, both of which are postulated to reach their catalytically active states through complex mechanisms that involve large domains movements, change in base pairing patterns and direct participation of divalent metal ions. In the case of L1 ligase, we reveal the structural basis of its allosteric control that involves an 80 angstrom swing of one of its stems, as well as the role of a flexible active site toward providing catalytic selectivity. In the case of Hammerhead ribozyme, we characterize the conformation and dynamics of several constructs in different ionic environments that lead to catalysis.en-USConformational transitionRibozymeRNARNA World hypothesisChemistryThesis or Dissertation