Computational design of RNAs with complex energy landscapes

Authors

  • Christian Höner zu Siederdissen,

    1. Department of Theoretical Chemistry, University of Vienna, A-1090 Wien, Austria
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  • Stefan Hammer,

    1. Department of Theoretical Chemistry, University of Vienna, A-1090 Wien, Austria
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  • Ingrid Abfalter,

    1. Research Support, Johannes Kepler University Linz, 4040 Linz, Austria
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  • Ivo L. Hofacker,

    1. Department of Theoretical Chemistry, University of Vienna, A-1090 Wien, Austria
    2. Bioinformatics and Computational Biology Research Group, University of Vienna, Vienna, Austria
    3. Center for Non-coding RNA in Technology and Health, University of Copenhagen, DK-1870 Frederiksberg, Denmark
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  • Christoph Flamm,

    1. Department of Theoretical Chemistry, University of Vienna, A-1090 Wien, Austria
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  • Peter F. Stadler

    Corresponding author
    1. Center for Non-coding RNA in Technology and Health, University of Copenhagen, DK-1870 Frederiksberg, Denmark
    2. Department of Computer Science and Interdisciplinary Center for Bioinformatics, Bioinformatics Group, Leipzig, Germany
    3. Max Planck Institute for Mathematics in the Sciences, Inselstraße 22, Leipzig, Germany
    4. RNomics Group, Fraunhofer Institut für Zelltherapie und Immunologie, Leipzig, Germany
    5. Santa Fe Institute, Santa Fe, NM
    • Department of Theoretical Chemistry, University of Vienna, A-1090 Wien, Austria
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  • This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

Correspondence to: Peter Stadler; e-mail: studla@bioinf.uni-leipzig.de

ABSTRACT

RNA has become an integral building material in synthetic biology. Dominated by their secondary structures, which can be computed efficiently, RNA molecules are amenable not only to in vitro and in vivo selection, but also to rational, computation-based design. While the inverse folding problem of constructing an RNA sequence with a prescribed ground-state structure has received considerable attention for nearly two decades, there have been few efforts to design RNAs that can switch between distinct prescribed conformations. We introduce a user-friendly tool for designing RNA sequences that fold into multiple target structures. The underlying algorithm makes use of a combination of graph coloring and heuristic local optimization to find sequences whose energy landscapes are dominated by the prescribed conformations. A flexible interface allows the specification of a wide range of design goals. We demonstrate that bi- and tri-stable “switches” can be designed easily with moderate computational effort for the vast majority of compatible combinations of desired target structures. RNAdesign is freely available under the GPL-v3 license. © 2013 Wiley Periodicals, Inc. Biopolymers 99: 1124–1136, 2013.

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