Abstract
We address a biochemical folding obstacle of “polymerase trapping” that arises in the remarkable RNA origami tile design framework of Geary, Rothemund and Andersen (Science 2014). We present a combinatorial formulation of this obstacle, together with an optimisation procedure that yields designs minimising the risk of encountering the corresponding topological trap in the tile folding phase. The procedure has been embedded in an automated software pipeline, and we provide examples of designs produced by the software, including an optimised version of the RNA smiley-face tile proposed by Geary and Andersen (DNA 2014).
Research supported by Academy of Finland grant 311639, “Algorithmic Designs for Biomolecular Nanostructures (ALBION)”.
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Notes
- 1.
We are currently working on the challenge of transforming the secondary-structure descriptions to actual RNA sequences, but lab-proof sequence design is a nontrivial task, and validating that the generated sequences really fold as intended requires experimental work.
- 2.
A spanning tree of a graph is a cycle-free subset of the graph that includes all the vertices of the graph [2, Chap. 23].
- 3.
This standard graph algorithm technique is discussed e.g. in [2, Sect. 35.2].
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Acknowledgments
We thank Ebbe Andersen and Cody Geary for introducing us to the problem of polymerase trapping in RNA origami tile design, and their encouragement to proceed with the solution approach discussed in this paper.
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Mohammed, A., Orponen, P., Pai, S. (2018). Algorithmic Design of Cotranscriptionally Folding 2D RNA Origami Structures. In: Stepney, S., Verlan, S. (eds) Unconventional Computation and Natural Computation. UCNC 2018. Lecture Notes in Computer Science(), vol 10867. Springer, Cham. https://doi.org/10.1007/978-3-319-92435-9_12
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