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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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.
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.
Seeman, N. C. Nucleic acid junctions and lattices. J. Theor. Biol. 99, 237–247 (1982).
Pinheiro, A. V., Han, D., Shih, W. M. & Yan, H. Challenges and opportunities for structural DNA nanotechnology. Nat. Nanotechnol. 6, 763–772 (2011).
Dey, S. et al. DNA origami. Nat. Rev. Methods Prim. 1, 13 (2021).
Douglas, S. M. et al. Rapid prototyping of 3D DNA-origami shapes with caDNAno. Nucleic Acids Res. 37, 5001–5006 (2009).
Williams, S. et al. Tiamat: a three-dimensional editing tool for complex DNA structures. 14th International Meeting on DNA Computing (Springer, 2008).
Benson, E. et al. Computer-aided production of scaffolded DNA nanostructures from flat sheet meshes. Angew. Chem. 55, 8869–8872 (2016).
Benson, E. et al. DNA rendering of polyhedral meshes at the nanoscale. Nature 523, 441 (2015).
de Llano, E. et al. Adenita: interactive 3D modelling and visualization of DNA nanostructures. Nucleic Acids Res. 48, 8269–8275 (2020).
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).
Jun, H., Wang, X., Bricker, W. P., Jackson, S. & Bathe, M. Rapid prototyping of wireframe scaffolded DNA origami using ATHENA. Preprint at bioRxiv https://doi.org/10.1101/2020.02.09.940320 (2020).
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.
Glaser, M. et al. The art of designing DNA nanostructures with CAD software. Molecules 26, 2287 (2021).
Doye, J. P. et al. Coarse-graining DNA for simulations of DNA nanotechnology. Phys. Chem. Chem. Phys. 15, 20395–20414 (2013).
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).
Lee, J. Y. et al. Rapid computational analysis of DNA origami assemblies at near-atomic resolution. ACS Nano 15, 1002–1015 (2021).
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).
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).
Šulc, P. et al. Sequence-dependent thermodynamics of a coarse-grained DNA model. J. Chem. Phys. 137, 135101 (2012).
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).
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).
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).
Procyk, J., Poppleton, E. & Šulc, P. Coarse-grained nucleic acid–protein model for hybrid nanotechnology. Soft Matter 17, 3586–3593 (2021).
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).
Poppleton, E., Romero, R., Mallya, A., Rovigatti, L. & Šulc, P. OxDNA.org: a public webserver for coarse-grained simulations of DNA and RNA nanostructures. Nucleic Acids Res. 28, e72 (2021).
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).
Matthies, M. et al. Triangulated wireframe structures assembled using single-stranded DNA tiles. ACS Nano 13, 1839–1848 (2019).
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).
Yao, G. et al. Meta-DNA structures. Nat. Chem. 12, 1067–1075 (2020).
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).
Benson, E., Carrascosa Marzo, R., Bath, J. & Turberfield, A. J. Strategies for constructing and operating DNA origami linear actuators. Small 17, 2007704 (2021).
Wang, Y. et al. DNA origami penetration in cell spheroid tissue models is enhanced by wireframe design. Adv. Mater. 33, 2008457 (2021).
Pettersen, E. F. et al. UCSF Chimera—a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605–1612 (2004).
Goodman, R. P. et al. Rapid chiral assembly of rigid DNA building blocks for molecular nanofabrication. Science 310, 1661–1665 (2005).
Xu, Y. et al. Tunable nanoscale cages from self-assembling DNA and protein building blocks. ACS Nano 13, 3545–3554 (2019).
Yu, Z. et al. A self-regulating DNA rotaxane linear actuator driven by chemical energy. J. Am. Chem. Soc. 143, 13292–13298 (2021).
Harris, C. R. et al. Array programming with NumPy. Nature 585, 357–362 (2020).
matplotlib/matplotlib: REL: v3.5.1. Zenodo https://zenodo.org/record/5773480#.YhgKyBtlBH4 (2021).
Cock, P. J. et al. Biopython: freely available Python tools for computational molecular biology and bioinformatics. Bioinformatics 25, 1422–1423 (2009).
Scikit-learn: machine learning in Python https://jmlr.csail.mit.edu/papers/v12/pedregosa11a.html (2011).
McKerns, M. M., Strand, L., Sullivan, T., Fang, A. & Aivazis, M. A. G. Building a framework for predictive science. Preprint at https://arxiv.org/abs/1202.1056 (2012).
Matthies, M. ox-serve v. 1.0. Zenodo https://doi.org/10.5281/zenodo.4551173 (2021).
Doye, J. P. K. et al. The oxDNA coarse-grained model as a tool to simulate DNA origami. Preprint at https://arxiv.org/abs/2004.05052 (2020).
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).
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).
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).
Webb, B. & Sali, A. Comparative protein structure modeling using MODELLER. Curr. Protoc. Bioinformatics 5.6.1–5.6.30 (2016).
Gopinath, A. et al. Absolute and arbitrary orientation of single-molecule shapes. Science 371 (2021).
Tian, Y. et al. Ordered three-dimensional nanomaterials using DNA-prescribed and valence-controlled material voxels. Nat. Mater. 19, 789–796 (2020).
Kube, M. et al. Revealing the structures of megadalton-scale DNA complexes with nucleotide resolution. Nat. Commun. 11, 6229 (2020).
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.
The authors declare no competing interests.
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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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
OxView and oxDNA file format description, scripting examples, ANM-oxDNA simulation setup, trajectory analysis and Listings S1-S17.
Importing and simulating nanostructures in oxView
Building hybrid DNA-protein system in oxView
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). https://doi.org/10.1038/s41596-022-00688-5