pyOrigamiBreak is a software tool that automates DNA origami design optimization123. As input, pyOrigamiBreak parses an incomplete CadNano design with staples unbroken. From this incomplete design, pyOrigamiBreak calculates the optimal staple break positions and returns a completed design with these optimal breaks and a score report.
The staple break positions are chosen by predicting the probability an origami design folds accurately, which is the product of the probabilities of folding each staple. Using a Boltzmann distribution, probability is expressed in terms of the Gibbs free energy change between unfolded and folded staples. The total Gibbs free energy for each staple binding to the scaffold consists of three components:
- Meeting — unfavorable.
- Loop closure — unfavorable.
- Hybridization — favorable.
Thus, the scoring function selects the design that maximizes favorable hybridization while minimizing loop closure penalties. The first term (Meeting) relies solely on the scaffold and staple concentrations, and thus will not contribute to the selection of a design if experimental conditions are constant.
References
- Aksel, T., J. Navarro, E., Fong, N. & Douglas, S. M. Design principles for accurate folding of DNA origami. Proceedings of the National Academy of Sciences 121, e2406769121 (2024).
- douglaslab/pyOrigamiBreak. Douglas Lab (2026).
- Douglas, S. M. et al. Rapid prototyping of 3D DNA-origami shapes with caDNAno. Nucleic Acids Res 37, 5001–5006 (2009).