Book of Abstracts: Albany 2007
June 19-23 2007
Modeling structure and dynamics of RNA
Large RNA molecules fold in a hierarchical manner into complex structures in which the majority of structural elements are composed of A-form double helices. However, the overall three-dimensional structure, and often the functional properties as well, are determined by the structure and dynamics of small motifs such as internal loops, bulges and other junctions. As a result, RNA molecules do not adopt a well-defined structure, but rather populate an ensemble of constantly interconverting conformations. The timescales of motions present in a dynamic ensemble range from picoseconds for local librations to milliseconds and beyond for collective domain motions or conformational transitions between kinetically hindered sub-states. The understanding of such motional modes is fundamental to rationalize heterogeneous reaction trajectories and specific structural adaptation upon complexation with diverse interacting partners. Functionally relevant conformations however may only be populated transiently, representing only a tiny fraction of the overall ensemble, and hence suitable techniques must be developed to characterize such heterogeneous conformational ensembles. NMR spin relaxation experiments provide information for the local, picosecond timescale motions, while the measurement of residual dipolar couplings (RDCs) of partially aligned molecules probes motions up to the millisecond timescales. We describe a novel computational technique in which these experimental data can be efficiently used as ensemble-averaged restraints. This approach enables the determination of an equilibrium ensemble that represents accurately both the structure and the dynamics of RNA molecules.
Department of Chemistry,