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. 2009 Dec 30;38(5):1711–1722. doi: 10.1093/nar/gkp1054

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© The Author(s) 2009. Published by Oxford University Press.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Figure 1. — Three folding pathways for the (toy) RNA sequence S = GGGGGGCCCCCC, between the secondary structure A = .((.....)).. with free energy −1.40 kcal/mol and the structure B = ..(((...))). with −1.70 kcal/mol. The left panel of this figure depicts a (direct) folding pathway from A to B produced by our implementation of the Morgan–Higgs algorithm (6) to produce a (greedy) direct path. The middle panel depicts the indirect folding pathway produced by our implementation of the extension of Morgan–Higgs indirect algorithm to the Turner energy model. Note that the structure .(.........) contains the base pair (2, 12) which is present in neither A nor B. The right panel depicts a folding pathway from A to B produced by our RNAtabupath algorithm. Although RNAtabupath often yields indirect pathways, in this case, the pathway returned by RNAtabupath is direct. Note that the last three structures proposed by RNAtabupath are ...(.....).., ..((.....))., ..(((...)))., respectively, having free energy of 1.90, −1.40 −1.70 kcal/mol. This nucleation and zipping of the stem–loop is energetically more favorable than the alternative (not proposed by RNAtabupath), given by structures ....(...)..., ...((...)).., ..(((...)))., respectively, having free energy of 4.90, 1.60 and −1.70 kcal/mol. Secondary structures are indicated in the familiar (Vienna) dot bracket notation, while free energy in kcal/mol appears to the right of each structure. Free energies are determined by the program RNAeval from the Vienna RNA Package (27).