Center for Structural Biology of HIV RNA

Abstract (NMR, Computation and Dynamics Core) RNA is central to the function of diverse cellular processes, including many steps of HIV-1 viral replication. Characterization of RNA structure and dynamics at atomic resolution is essential for a full understanding of these functions, which derive in large part from its structural plasticity over a range of timescales. Despite this, there is a relative paucity of structural information for RNAs, which comprise <2% of structures deposited in the Protein Data Bank. NMR is an important tool in RNA structure determination, contributing ~35% of the deposited RNA structures, and is uniquely capable of probing RNA dynamics on functionally relevant timescales in solution. Computational techniques are also essential for reliable simulation of nucleic acids, integration of experimental data from different sources, and comparison of models with experimental data at increasingly long timescales. The NMR, Computation and Dynamics Core therefore brings together investigators from seven institutions who have extensive and complementary expertise in applying and developing leading edge techniques for studying the structure, interactions, and dynamics of RNA using NMR and advanced computational tools. Core investigators are developing methods to probe increasingly large RNAs, tag RNAs with unique isotopic labels, and determine the atomic resolution structures of RNA dynamic ensembles. These technologies will be applied to challenging RNA systems to illuminate the role of HIV-1 RNA structural complexes in viral transcription, splicing, nuclear export, translation, packaging, and particle assembly. In addition, the Core will provide general NMR screening services, including design and preparation of isotopically labeled RNAs, data acquisition and analysis, and will help all CRNA Research Projects make effective use of state-of-the-art tools in computational structure calculation and refinement.