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The inverse RNA folding problem for designing sequences that fold into a given RNA secondary structure was introduced in the early 1990's in Vienna. Using a coarse-grain tree graph representation of the RNA secondary structure, we extended the inverse RNA folding problem to include constraints such as thermodynamic stability and mutational robustness, developing a program called RNAexinv. In the next step, we formulated a fragment-based design approach of RNA sequences that can be useful to practitioners in a variety of biological applications. In this shape-based design approach, specific RNA structural motifs with known biological functions are strictly enforced while others can possess more flexibility in their structure in favor of preserving physical attributes and additional constraints. Our program is called RNAfbinv. Detection of riboswitches in genomic sequences using structure based methods, including the incorporation of RNAfbinv, will also be discussed.
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