Prof. Alain Laederach, Department of Biomedical Sciences & School of Public Health – SUNY Albany
Title: “Identifying RNA folding through kinetic model enumeration”
Large RNA molecules are known to fold through multiple parallel pathways to achieve their functional conformation. These pathways include stable intermediate structures that we identify using our KinFold algorithm (http://simtk.org/home/kinfold) for the analysis of time-resolved hydroxyl radical footprinting experiments. KinFold enumerates kinetic model topologies to determine the structure, lifetimes, and abundance of intermediates along the folding pathways of RNA. We are therefore able to identify the best fitting kinetic model for each folding reaction studied. We used this approach to study the folding of the L-21 T. thermophila group I intron, a catalytic ribozyme, at 6 temperatures ranging from 25° to 51° C. Our analysis of this data reveals that the rates for a majority of the transitions (between intermediate, folded and unfolded states) obey the Arrhenius equation, allowing us to estimate the relative energies of activation for inter conversion between the states of an RNA. Furthermore, we are able to estimate the lifetimes of the different intermediate structures. These results reveal a simple landscape, where folding of the peripheral elements of the RNA create significant barriers to folding. Our approach is unique in that it allows us to simultaneously estimate the activation energies for all transitions in an RNA folding reaction.
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