Folding functional RNA's: is it easier than folding proteins? Sebastian Doniach, Stanford University Abstract Genome sequencing is providing more and more examples of small functional RNA molecules encoded in the "non-coding" regions of genomic DNA. Elucidating structure-function relationships for these RNA's is seen to be of increasing importance in understanding cell biology. At the secondary structure level, RNA molecules are more stable than are the helices and sheets which constitute proteins, the building blocks for most cellular machines. However, experimental determination of RNA structural conformations is hampered by the large coulomb forces exerted by the phosphate backbone constitution of the polynucleotides, In this talk we will present recent advances in our ability to model structural conformations of RNA based on low resolution structural data obtained from small angle solution x-ray scattering (SAXS). A combination of sequence-based structure prediction for the junction regions of the RNA, and SAXS data for the 3-dimensional arrangement of the Crick-Watson helices, allows for building 3-dimensional models of the conformational changes induced by changing ionic conditions and by substrate binding. Such models can then provide a basis for studying the effects of mutations on the function of the RNA's.