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Design of RNA sequences with predefined conformational and kinetic properties

Abstract

The ability to accurately design molecules with predefined properties and functions is one of the key technologies to achieve progress in fields such as Syntetic Biology and Nanotechnology. RNA sequences that form bistable switches can be computed quite easily by using simple heuristics for a combinatorial optimization problem (Flamm et al. 2001). This is possible because theoretical results show that for any two secondary structures many sequences exist that are compatible with both. However, for more than more than two structures this is not the case. The design problem becomes even harder if particular kinetic folding properties are desired. We want to design RNA sequences that fold into more than two given secondary structures strictly following predefined conformational and kinetic properties. This will be achieved through an iterative process of sequence design, calculation and evaluation of the kinetic properties, and sequence optimization. The folding landscape is characterized using RNAsubopt (Hofacker et al. 1994), Barriers (Flamm et al. 2002) and Treekin (Wolfinger et al. 2004). The evaluation is done via curve sketching and numerical integration. To guarantee a fair and efficient sampling in the space of compatible sequences, the design problem has to be rephrased as a graph coloring problem (Abfalter 2005).
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