From Sequences to Shapes and Back: A Case Study in RNA Secondary Structures

Peter Schuster, Walter Fontana, Peter F. Stadler, and Ivo L. Hofacker

RNA folding is viewed as a map assigning secondary structures to sequences. At fixed chain length the number of sequences exceeds by far the number of structures. Frequencies of structures are highly non-uniform: we find relatively few common and many rare ones. Using an algorithm for inverse folding we show that sequences sharing the same structures are distributed randomly over sequences space. All common structures can be accessed from an arbitrary sequence by a number of mutations much smaller than the chain length. Evolutionary optimization has to search only a small fraction of all sequences in order to find a suitable target structure and thus could hardly miss it. The sequence space is percoated by extensive neutral networks connecting nearest neighbours folding into identical structures.

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