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Nucleic acid helix structure determination from NMR proton chemical shifts

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Abstract

We present a method for de novo derivation of the three-dimensional helix structure of nucleic acids using non-exchangeable proton chemical shifts as sole source of experimental restraints. The method is called chemical shift de novo structure derivation protocol employing singular value decomposition (CHEOPS) and uses iterative singular value decomposition to optimize the structure in helix parameter space. The correct performance of CHEOPS and its range of application are established via an extensive set of structure derivations using either simulated or experimental chemical shifts as input. The simulated input data are used to assess in a defined manner the effect of errors or limitations in the input data on the derived structures. We find that the RNA helix parameters can be determined with high accuracy. We finally demonstrate via three deposited RNA structures that experimental proton chemical shifts suffice to derive RNA helix structures with high precision and accuracy. CHEOPS provides, subject to further development, new directions for high-resolution NMR structure determination of nucleic acids.

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Acknowledgments

The 6th framework program of the EU, project FSG-V-RNA, is acknowledged for funding.

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Authors and Affiliations

  1. Department of Biophysical Chemistry, Institute of Molecules and Materials, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ, Nijmegen, The Netherlands

    Ramon M. van der Werf, Marco Tessari & Sybren S. Wijmenga

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  1. Ramon M. van der Werf
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  2. Marco Tessari
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  3. Sybren S. Wijmenga
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Correspondence to Sybren S. Wijmenga.

Additional information

Software Available: NUCHEMICS and the python script, CHEOPS, are available upon request. 3DNA can be obtained via the website: http://adna.rutgers.edu.

Electronic supplementary material

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10858_2013_9725_MOESM1_ESM.pdf

Details on calculation procedures, including analysis of chemical shift optimized and deposited structures (RMSDs, helix parameters etc.). (PDF 1672 kb)

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van der Werf, R.M., Tessari, M. & Wijmenga, S.S. Nucleic acid helix structure determination from NMR proton chemical shifts. J Biomol NMR 56, 95–112 (2013). https://doi.org/10.1007/s10858-013-9725-y

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