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


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.

Data availability

The input files for examples in this protocols are available in the examples directory ( and in Supplementary Data.

Code availability

All source code presented in this protocol are freely available under a GNU Public License at The Python analysis scripts used for analysis are available under GNU Public License at The oxDNA simulation code and documentation are available from The DNA/RNA–protein version of the model is in a separate branch available at A bleeding-edge version of oxDNA that will replace the main branch at some point in the future can be found at


  1. Seeman, N. C. Nucleic acid junctions and lattices. J. Theor. Biol. 99, 237–247 (1982).

    CAS  Article  Google Scholar 

  2. Pinheiro, A. V., Han, D., Shih, W. M. & Yan, H. Challenges and opportunities for structural DNA nanotechnology. Nat. Nanotechnol. 6, 763–772 (2011).

    CAS  Article  Google Scholar 

  3. Dey, S. et al. DNA origami. Nat. Rev. Methods Prim. 1, 13 (2021).

    Article  Google Scholar 

  4. Douglas, S. M. et al. Rapid prototyping of 3D DNA-origami shapes with caDNAno. Nucleic Acids Res. 37, 5001–5006 (2009).

    CAS  Article  Google Scholar 

  5. Williams, S. et al. Tiamat: a three-dimensional editing tool for complex DNA structures. 14th International Meeting on DNA Computing (Springer, 2008).

  6. Benson, E. et al. Computer-aided production of scaffolded DNA nanostructures from flat sheet meshes. Angew. Chem. 55, 8869–8872 (2016).

    CAS  Article  Google Scholar 

  7. Benson, E. et al. DNA rendering of polyhedral meshes at the nanoscale. Nature 523, 441 (2015).

    CAS  Article  Google Scholar 

  8. de Llano, E. et al. Adenita: interactive 3D modelling and visualization of DNA nanostructures. Nucleic Acids Res. 48, 8269–8275 (2020).

    Article  Google Scholar 

  9. Huang, C.-M., Kucinic, A., Johnson, J. A., Su, H.-J. & Castro, C. E. Integrated computer-aided engineering and design for DNA assemblies. Nat. Mater. 20, 1264–1271 (2021).

    CAS  Article  Google Scholar 

  10. Jun, H., Wang, X., Bricker, W. P., Jackson, S. & Bathe, M. Rapid prototyping of wireframe scaffolded DNA origami using ATHENA. Preprint at bioRxiv (2020).

  11. Doty, D., Lee, B. L. & Stérin, T. scadnano: a browser-based, scriptable tool for designing DNA nanostructures. 26th International Conference on DNA Computing and Molecular Programming (DNA 26), 2020.

  12. Glaser, M. et al. The art of designing DNA nanostructures with CAD software. Molecules 26, 2287 (2021).

    CAS  Article  Google Scholar 

  13. Doye, J. P. et al. Coarse-graining DNA for simulations of DNA nanotechnology. Phys. Chem. Chem. Phys. 15, 20395–20414 (2013).

    CAS  Article  Google Scholar 

  14. Maffeo, C. & Aksimentiev, A. MrDNA: a multi-resolution model for predicting the structure and dynamics of DNA systems. Nucleic Acids Res. 48, 5135–5146 (2020).

    CAS  Article  Google Scholar 

  15. Lee, J. Y. et al. Rapid computational analysis of DNA origami assemblies at near-atomic resolution. ACS Nano 15, 1002–1015 (2021).

    CAS  Article  Google Scholar 

  16. Kim, D.-N., Kilchherr, F., Dietz, H. & Bathe, M. Quantitative prediction of 3D solution shape and flexibility of nucleic acid nanostructures. Nucleic Acids Res. 40, 2862–2868 (2011).

    Article  Google Scholar 

  17. Snodin, B. E. et al. Introducing improved structural properties and salt dependence into a coarse-grained model of DNA. J. Chem. Phys. 142, 06B613_1 (2015).

    Article  Google Scholar 

  18. Šulc, P. et al. Sequence-dependent thermodynamics of a coarse-grained DNA model. J. Chem. Phys. 137, 135101 (2012).

    Article  Google Scholar 

  19. Rovigatti, L., Šulc, P., Reguly, I. Z. & Romano, F. A comparison between parallelization approaches in molecular dynamics simulations on GPUs. J. Comput. Chem. 36, 1–8 (2015).

    CAS  Article  Google Scholar 

  20. Ouldridge, T. E., Louis, A. A. & Doye, J. P. Structural, mechanical, and thermodynamic properties of a coarse-grained DNA model. J. Chem. Phys. 134, 02B627 (2011).

    Article  Google Scholar 

  21. Šulc, P., Romano, F., Ouldridge, T. E., Doye, J. P. & Louis, A. A. A nucleotide-level coarse-grained model of RNA. J. Chem. Phys. 140, 235102 (2014).

    Article  Google Scholar 

  22. Procyk, J., Poppleton, E. & Šulc, P. Coarse-grained nucleic acid–protein model for hybrid nanotechnology. Soft Matter 17, 3586–3593 (2021).

    CAS  Article  Google Scholar 

  23. Suma, A. et al. TacoxDNA: a user-friendly web server for simulations of complex DNA structures, from single strands to origami. J. Comput. Chem. 40, 2586–2595 (2019).

    CAS  Article  Google Scholar 

  24. Poppleton, E., Romero, R., Mallya, A., Rovigatti, L. & Šulc, P. a public webserver for coarse-grained simulations of DNA and RNA nanostructures. Nucleic Acids Res. 28, e72 (2021).

    Google Scholar 

  25. Poppleton, E. et al. Design, optimization and analysis of large DNA and RNA nanostructures through interactive visualization, editing and molecular simulation. Nucleic Acids Res. 49, W491–W498 (2020).

    Article  Google Scholar 

  26. Matthies, M. et al. Triangulated wireframe structures assembled using single-stranded DNA tiles. ACS Nano 13, 1839–1848 (2019).

    CAS  PubMed  Google Scholar 

  27. Hong, F., Schreck, J. S. & Šulc, P. Understanding DNA interactions in crowded environments with a coarse-grained model. Nucleic Acids Res. 48, 10726–10738 (2020).

    CAS  Article  Google Scholar 

  28. Yao, G. et al. Meta-DNA structures. Nat. Chem. 12, 1067–1075 (2020).

    CAS  Article  Google Scholar 

  29. Wang, Y., Baars, I., Fördös, F. & Högberg, B. Clustering of death receptor for apoptosis using nanoscale patterns of peptides. ACS Nano 15, 9614–9626 (2021).

    Article  Google Scholar 

  30. Benson, E., Carrascosa Marzo, R., Bath, J. & Turberfield, A. J. Strategies for constructing and operating DNA origami linear actuators. Small 17, 2007704 (2021).

    CAS  Article  Google Scholar 

  31. Wang, Y. et al. DNA origami penetration in cell spheroid tissue models is enhanced by wireframe design. Adv. Mater. 33, 2008457 (2021).

    CAS  Article  Google Scholar 

  32. Pettersen, E. F. et al. UCSF Chimera—a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605–1612 (2004).

    CAS  Article  Google Scholar 

  33. Goodman, R. P. et al. Rapid chiral assembly of rigid DNA building blocks for molecular nanofabrication. Science 310, 1661–1665 (2005).

    CAS  Article  Google Scholar 

  34. Xu, Y. et al. Tunable nanoscale cages from self-assembling DNA and protein building blocks. ACS Nano 13, 3545–3554 (2019).

    CAS  Article  Google Scholar 

  35. Yu, Z. et al. A self-regulating DNA rotaxane linear actuator driven by chemical energy. J. Am. Chem. Soc. 143, 13292–13298 (2021).

    CAS  Article  Google Scholar 

  36. Harris, C. R. et al. Array programming with NumPy. Nature 585, 357–362 (2020).

    CAS  Article  Google Scholar 

  37. matplotlib/matplotlib: REL: v3.5.1. Zenodo (2021).

  38. Cock, P. J. et al. Biopython: freely available Python tools for computational molecular biology and bioinformatics. Bioinformatics 25, 1422–1423 (2009).

    CAS  Article  Google Scholar 

  39. Scikit-learn: machine learning in Python (2011).

  40. McKerns, M. M., Strand, L., Sullivan, T., Fang, A. & Aivazis, M. A. G. Building a framework for predictive science. Preprint at (2012).

  41. Matthies, M. ox-serve v. 1.0. Zenodo (2021).

  42. Doye, J. P. K. et al. The oxDNA coarse-grained model as a tool to simulate DNA origami. Preprint at (2020).

  43. Sengar, A., Ouldridge, T. E., Henrich, O., Rovigatti, L. & Šulc, P. A primer on the oxDNA model of DNA: when to use it, how to simulate it and how to interpret the results. Front. Mol. Biosci. 8, 551 (2021).

    Article  Google Scholar 

  44. Jo, S., Kim, T., Iyer, G. V. & Im, W. CHARMM-GUI: a web-based graphical user interface for CHARMM. J. Comput. Chem. 29, 1859–1865 (2008).

    CAS  Article  Google Scholar 

  45. Berendsen, H. J. C., van der Spoel, D. & van Drunen, R. GROMACS: a message-passing parallel molecular dynamics implementation. Comput. Phys. Commun. 91, 43–56 (1995).

    CAS  Article  Google Scholar 

  46. Webb, B. & Sali, A. Comparative protein structure modeling using MODELLER. Curr. Protoc. Bioinformatics 5.6.1–5.6.30 (2016).

  47. Gopinath, A. et al. Absolute and arbitrary orientation of single-molecule shapes. Science 371 (2021).

  48. Tian, Y. et al. Ordered three-dimensional nanomaterials using DNA-prescribed and valence-controlled material voxels. Nat. Mater. 19, 789–796 (2020).

    CAS  Article  Google Scholar 

  49. Kube, M. et al. Revealing the structures of megadalton-scale DNA complexes with nucleotide resolution. Nat. Commun. 11, 6229 (2020).

    CAS  Article  Google Scholar 

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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

Authors and Affiliations



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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Peer review information

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):

Yao, G. et al. Nat. Chem. 12, 1067–1075 (2020):

Procyk, J. et al. Soft Matter 17, 3586–3593 (2021):

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 (2022).

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