Models and simulations of structural DNA nanotechnology reveal fundamental principles of self-assembly

DNA is not only a centrally important molecule in biology: the specificity of bonding that allows it to be the primary information storage medium for life has also allowed it to become one of the most promising materials for designing intricate, self-assembling structures at the nanoscale. While the applications of these structures are both broad and highly promising, the self-assembly process itself has attracted interest not only for the practical applications of designing structures with more efficient assembly pathways, but also due to a desire to understand the principles underlying self-assembling systems more generally, of which DNA-based systems provide intriguing and unique examples. Here, we review the fundamental physical principles that underpin the self-assembly process in the field of DNA nanotechnology, with a specific focus on simulation and modelling and what we can learn from them. In particular, we compare and contrast DNA origami and bricks and briefly outline other approaches, with an overview of concepts such as cooperativity, nucleation and hysteresis; we also explain how nucleation barriers can be controlled and why they can be helpful in ensuring error-free assembly. While high-resolution models may be needed to obtain accurate system-specific properties, often very simple coarse-grained models are sufficient to extract the fundamentals of the underlying physics and can enable us to gain deep insight. By combining experimental and simulation approaches to understand the details of the self-assembly process, we can optimise its yields and fidelity, which may in turn facilitate its use in practical applications.