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Abstract:

As detailed structural characterizations of large complex DNA nanostructures are hard to obtain experimentally, particularly if they have substantial flexibility, coarse-grained modeling can potentially provide an important complementary role. Such modeling can provide a detailed view of both the average structure and the structural fluctuations, as well as providing insight into how the nanostructure's design determines its structural properties. Here, we present a case study of jointed DNA nanostructures using the oxDNA model. In particular, we consider archetypal hinge and sliding joints, as well as more complex structures involving a number of such coupled joints. Our results highlight how the nature of the motion in these structures can sensitively depend on the precise details of the joints. Furthermore, the generally good agreement with experiments illustrates the power of this approach and suggests the use of such modeling to prescreen the properties of putative designs.

Abstract:

It is well established that gene regulation can be achieved through activator and repressor proteins that bind to DNA and switch particular genes on or off, and that complex metabolic networks determine the levels of transcription of a given gene at a given time. Using three complementary computational techniques to study the sequence-dependence of DNA denaturation within DNA minicircles, we have observed that whenever the ends of the DNA are constrained, information can be transferred over long distances directly by the transmission of mechanical stress through the DNA itself, without any requirement for external signalling factors. Our models combine atomistic molecular dynamics (MD) with coarse-grained simulations and statistical mechanical calculations to span three distinct spatial resolutions and timescale regimes. While they give a consensus view of the non-locality of sequence-dependent denaturation in highly bent and supercoiled DNA loops, each also reveals a unique aspect of long-range informational transfer that occurs as a result of restraining the DNA within the closed loop of the minicircles.

Abstract:

We use oxDNA, a coarse-grained model of DNA at the nucleotide level, to simulate large nanoprisms that are composed of multi-arm star tiles, in which the size of bulge loops that have been incorporated into the tile design are used to control the flexibility of the tiles. The oxDNA model predicts equilibrium structures for several different nanoprism designs that are in excellent agreement with the experimental structures as measured by cryoTEM. In particular we reproduce the chiral twisting of the top and bottom faces of the nanoprisms as the bulge sizes in these structures are varied due to the greater flexibility of larger bulges. We are also able to follow how the properties of the star tiles evolve as the prisms are assembled. Individual star tiles are very flexible, but their structures become increasingly well-defined and rigid as they are incorporated into larger assemblies. oxDNA also finds that the experimentally observed prisms are more stable than their inverted counterparts, but interestingly this preference for the arms of the tiles to bend in a given direction only emerges after they are part of larger assemblies. These results show the potential for oxDNA to provide detailed structural insight as well as to predict the properties of DNA nanostructures, and hence to aid rational design in DNA nanotechnology.