Things on the nanoscale are, by definition, quite small. This poses a problem in the sense that it can be tricky to get a good look at them. Microscopes can only get you so far; although microscopy techniques are constantly improving it is still much easier (and significantly cheaper) to simulate your design at whatever level of detail you require, especially if you want to see things moving around.

It is not obvious, however, what level of detail is suitable. Perhaps you need to include every single atom in your model (which would require a huge amount of computing power), or maybe it is enough to model each helix as beads on a string, or simply a rigid rod (which would be much less realistic).

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Different level of details, from all-atom, to oxDNA, to a string of beads

 

For DNA origami it is usually enough to simulate at the level of nucleotides. That way, you get the dynamics of single strands hybridising to form double helices (or melting apart at higher temperatures), but you don’t have to calculate every single atom.

One very successful simulation model, doing precisely that, is called oxDNA and was developed here in Oxford. The model was originally written by Tom Ouldridge during his PhD (or rather DPhil as it’s called here) studies. It has since then been improved and extended by multiple members of the Doye and Louis groups and used in close to a hundred publications. Nucleotides in oxDNA are modelled as rigid bodies with four interaction sites: a backbone and a base repulsion site, both to model excluded volume, plus a stacking site and a hydrogen bonding site in order to form the duplex.

 

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Forces between the nucleotide interaction sites

The model can be simulated by either molecular dynamics or by Monte Carlo simulation. In molecular dynamics (MD), the forces experienced between the nucleotides are integrated over time with a given timestep, updating velocities and positions accordingly. On the other hand, in Monte Carlo (MC) simulation, the state of the system is changed in rotational and translational moves of different probability, allowing for a better exploration of the state space. You can then try changing parameters such as the temperature or the salt concentration to see how it affects your structure.

Many researchers design their structures in caDNAno, a DNA origami design software, but it is possible to convert cadnano files (and many other input formats) into the oxDNA representation, using tools such as tacoxdna. To look at your system you can load the oxDNA files into a visualizer such as oxView, which I am developing together with the Arizona State University.

Sometimes, the structure doesn’t look quite right freshly converted from caDNAno. This is because you can only draw your design on a lattice, with all helices parallel to each other. If this is the case, you can also use oxView to edit and re-arrange your DNA design before starting to simulate, as seen in the example below:

 

In conclusion, if a nanostructure looks small, try using your scroll wheel to zoom 🙂

 

Written by Joakim Bohlin, University of Oxford

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