The oxDNA Coarse-Grained Model as a Tool to Simulate DNA Origami.

This chapter introduces how to run molecular dynamics simulations for DNA origami using the oxDNA coarse-grained model.

Computing the Elastic Mechanical Properties of Rodlike DNA Nanostructures.

To study the elastic properties of rodlike DNA nanostructures, we perform long simulations of these structures using the oxDNA coarse-grained model. By analyzing the fluctuations in these trajectories, we obtain estimates of the bend and twist persistence lengths and the underlying bend and twist elastic moduli and couplings between them. Only on length scales beyond those associated with the spacings between the interhelix crossovers do the bending fluctuations behave like those of a wormlike chain. The obtained bending persistence lengths are much larger than that for double-stranded DNA and increase nonlinearly with the number of helices, whereas the twist moduli increase approximately linearly. To within the numerical error in our data, the twist-bend coupling constants are of order zero. That the bending persistence lengths that we obtain are generally somewhat higher than in experiment probably reflects both that the simulated origamis have no assembly defects and that the oxDNA extensional modulus for double-stranded DNA is too large.

Chiral shape fluctuations and the origin of chirality in cholesteric phases of DNA origamis.

Lyotropic cholesteric liquid crystal phases are ubiquitously observed in biological and synthetic polymer solutions, characterized by a complex interplay between thermal fluctuations and entropic and enthalpic forces. The elucidation of the link between microscopic features and macroscopic chiral structure, and of the relative roles of these competing contributions on phase organization, remains a topical issue. Here, we provide theoretical evidence of a previously unidentified mechanism of chirality amplification in lyotropic liquid crystals, whereby phase chirality is governed by fluctuation-stabilized helical deformations in the conformations of their constituent molecules. Our results compare favorably to recent experimental studies of DNA origami assemblies and demonstrate the influence of intramolecular mechanics on chiral supramolecular order, with potential implications for a broad class of experimentally relevant colloidal systems.

Design and synthesis of pleated DNA origami nanotubes with adjustable diameters.

DNA origami allows for the synthesis of nanoscale structures and machines with nanometre precision and high yields. Tubular DNA origami nanostructures are particularly useful because their geometry facilitates a variety of applications including nanoparticle encapsulation, the construction of artificial membrane pores and as structural scaffolds that can uniquely spatially arrange nanoparticles in circular, linear and helical arrays. Here we report a system of parametrization for the design of radially symmetric DNA origami nanotubes with adjustable diameter, length, crossover density, pleat angle and chirality. The system is implemented into a computational algorithm that provides a practical means to navigate the complex geometry of DNA origami nanotube design. We apply this in the design, synthesis and characterization of novel DNA origami nanotubes. These include structures with pleated walls where the same number of duplexes can form nanotubes with different diameters, and to vary the diameter within the same structure. We also construct nanotubes that can be reconfigured into different chiral shapes. Finally, we explore the effect of strain on the local and global geometry of DNA origami nanotubes and demonstrate how pleated walls can provide a strategy to rigidify nanotubes and to construct closely packed parallel duplexes.

Rolling circle amplification shows a sinusoidal template length-dependent amplification bias.

Biophysical properties of DNA such as its longitudinal and torsional persistence length govern many processes and phenomena in biology, DNA nanotechnology and biotechnology. It has, for example, long been known that the circularization efficiency of short DNA fragments shows a periodic pattern where fragments with integer helical turns circularize much more efficiently than those with odd helical half turns due to stronger stacking of duplex ends. Small DNA circles can serve as templates for rolling circle amplification (RCA), which is a common and extremely robust amplification mechanism for nucleic acids. We discovered a strong template length-dependent amplification efficiency bias of RCA with the same periodicity as B-DNA. However, stacking cannot explain the mechanism behind this bias as the presence of the polymerase in the bifurcation fork inhibits base stacking of ends. Instead, coarse-grained molecular dynamics simulations imply that different amplification efficiencies come from a varying fraying probability of the last two downstream base pairs. We conclude that an increased strain-promoted fraying probability can increase the polymerization rate compared to a relaxed template.