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Atomic accuracy in predicting and designing noncanonical RNA structure

Nature Methods volume 7, pages 291–294 (2010)Cite this article

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Abstract

We present fragment assembly of RNA with full-atom refinement (FARFAR), a Rosetta framework for predicting and designing noncanonical motifs that define RNA tertiary structure. In a test set of thirty-two 6–20-nucleotide motifs, FARFAR recapitulated 50% of the experimental structures at near-atomic accuracy. Sequence redesign calculations recovered native bases at 65% of residues engaged in noncanonical interactions, and we experimentally validated mutations predicted to stabilize a signal recognition particle domain.

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Figure 1: De novo modeling of noncanonical RNA structure with FARFAR.
Figure 2: Computational and experimental tests validating sequence design and thermostabilization.

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Acknowledgements

We thank contributors to the current Rosetta codebase, local computer administrators D. Alonso and K. Laidig, the BioX2 cluster (US National Science Foundation award CNS-0619926) and TeraGrid computing resources for enabling rapid development of macromolecular modeling methods; and K. Sjölander for suggesting the acronym FARFAR. This work was supported by the Jane Coffin Childs and Burroughs-Wellcome Foundations (R.D.), the Damon Runyon Cancer Research Foundation (J.K.) and the Howard Hughes Medical Institute (D.B.).

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Authors and Affiliations

  1. Departments of Biochemistry and Physics, Stanford University, Stanford, California, USA

    Rhiju Das

  2. Center for Bioinformatics and Department of Molecular Biosciences, The University of Kansas, Lawrence, Kansas, USA

    John Karanicolas

  3. Department of Biochemistry, Howard Hughes Medical Institute and University of Washington, Seattle, Washington, USA

    David Baker

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  1. Rhiju Das
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  2. John Karanicolas
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Contributions

R.D. designed research, implemented the method, analyzed data and prepared the manuscript; J.K. designed research and implemented the method; and D.B. designed research.

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Correspondence to Rhiju Das or David Baker.

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The authors declare no competing financial interests.

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Supplementary Figures 1–9 and Supplementary Tables 1–3 (PDF 6340 kb)

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Das, R., Karanicolas, J. & Baker, D. Atomic accuracy in predicting and designing noncanonical RNA structure. Nat Methods 7, 291–294 (2010). https://doi.org/10.1038/nmeth.1433

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