Design of multistable RNA molecules

We show that the problem of designing RNA sequences that can fold into mult iple stable secondary structures can be transformed into a combinatorial op timization problem that can be solved by means of simple heuristics. Hence it is feasible to design RNA switches with prescribed structural alternativ es. We discuss the theoretical background and present an efficient tool tha t allows the design of various types of switches. We argue that both the ge neral properties of the sequence structure map of RNA secondary structures and the ease with which our design tool finds bistable RNAs strongly indica tes that RNA switches are easily accessible in evolution. Thus conformation al switches are yet another function for which RNA can be employed.