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Design and simulation of DNA, RNA and hybrid protein–nucleic acid nanostructures with oxView

Nature Protocols volume 17, pages 1762–1788 (2022)Cite this article

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Abstract

Molecular simulation has become an integral part of the DNA/RNA nanotechnology research pipeline. In particular, understanding the dynamics of structures and single-molecule events has improved the precision of nanoscaffolds and diagnostic tools. Here we present oxView, a design tool for visualization, design, editing and analysis of simulations of DNA, RNA and nucleic acid–protein nanostructures. oxView provides an accessible software platform for designing novel structures, tweaking existing designs, preparing them for simulation in the oxDNA/RNA molecular simulation engine and creating visualizations of simulation results. In several examples, we present procedures for using the tool, including its advanced features that couple the design capabilities with a coarse-grained simulation engine and scripting interface that can programmatically edit structures and facilitate design of complex structures from multiple substructures. These procedures provide a practical basis from which researchers, including experimentalists with limited computational experience, can integrate simulation and 3D visualization into their existing research programs.

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Fig. 1: Importing and assembling designs created in caDNAno.
Fig. 2: Designing a DNA tetrahedron using the oxView editing tools.
Fig. 3: Editing tools available in oxView.
Fig. 4: Interactive simulation in oxServe.
Fig. 5: Examples of using the oxView scripting interface.
Fig. 6: oxView visualization of a bluetongue virus core and a DNA origami barrel.
Fig. 7: Various stages of construction of a protein–DNA hybrid in oxView.

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Data availability

The input files for examples in this protocols are available in the examples directory (github.com/sulcgroup/oxdna-viewer/tree/master/examples) and in Supplementary Data.

Code availability

All source code presented in this protocol are freely available under a GNU Public License at github.com/sulcgroup/oxdna-viewer. The Python analysis scripts used for analysis are available under GNU Public License at github.com/sulcgroup/oxdna_analysis_tools. The oxDNA simulation code and documentation are available from dna.physics.ox.ac.uk. The DNA/RNA–protein version of the model is in a separate branch available at https://github.com/sulcgroup/anm-oxdna. A bleeding-edge version of oxDNA that will replace the main branch at some point in the future can be found at github.com/lorenzo-rovigatti/oxDNA.

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Acknowledgements

We acknowledge support from NSF grant 1931487 and ONR grant N000142012094. This project has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 765703 (to J.B.). We thank users of the tool for their helpful feedback and bug reports, and members of Yan and Šulc labs at ASU and Doye, Louis and Turberfield labs in Oxford for testing the tool.

Author information

Author notes

  1. These authors contributed equally: Joakim Bohlin, Michael Matthies, Erik Poppleton, Jonah Procyk.

Authors and Affiliations

  1. Clarendon Laboratory, Department of Physics, University of Oxford, Oxford, UK

    Joakim Bohlin

  2. School of Molecular Sciences and Center for Molecular Design and Biomimetics, The Biodesign Institute, Arizona State University, Tempe, AZ, USA

    Michael Matthies, Erik Poppleton, Jonah Procyk, Aatmik Mallya, Hao Yan & Petr Šulc

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Contributions

J.B., M.M., E.P. and J.P. contributed equally to this paper in code, testing and manuscript preparation, and their author order was determined alphabetically. J.B., M.M., E.P., J.P. and A.M. all contributed significantly to the oxView codebase since the previous publication on oxView. H.Y. contributed expertise in DNA nanotechnology and advised on the development of the tool. P.Š. designed and supervised the research tools development. All authors discussed the results and wrote the paper.

Corresponding author

Correspondence to Petr Šulc.

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The authors declare no competing interests.

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Nature Protocols thanks David Doty, Manish K. Gupta and Christopher Maffeo for their contribution to the peer review of this work.

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Related links

Key references using this protocol

Poppleton, E. et al. Nucleic Acids Res. 48, e72 (2020): https://doi.org/10.1093/nar/gkaa417

Yao, G. et al. Nat. Chem. 12, 1067–1075 (2020): https://doi.org/10.1038/s41557-020-0539-8

Procyk, J. et al. Soft Matter 17, 3586–3593 (2021): https://doi.org/10.1039/D0SM01639J

Supplementary information

Supplementary Information

OxView and oxDNA file format description, scripting examples, ANM-oxDNA simulation setup, trajectory analysis and Listings S1-S17.

Supplementary Video 1

Importing and simulating nanostructures in oxView

Supplementary Video 2

Building hybrid DNA-protein system in oxView

Supplementary Data

Source codes of files for respective protocols, along with examples of expected outcomes

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Bohlin, J., Matthies, M., Poppleton, E. et al. Design and simulation of DNA, RNA and hybrid protein–nucleic acid nanostructures with oxView. Nat Protoc 17, 1762–1788 (2022). https://doi.org/10.1038/s41596-022-00688-5

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