Modelling DNA origami self-assembly at the domain level

Abstract

We present a modelling framework, and basic model parameterization, for the study of DNA origami folding at the level of DNA domains. Our approach is explicitly kinetic and does not assume a specific folding pathway. The binding of each staple is associated with a free-energy change that depends on staple sequence, the possibility of coaxial stacking with neighbouring domains, and the entropic cost of constraining the scaffold by inserting staple crossovers. A rigorous thermodynamic model is difficult to implement as a result of the complex, multiply connected geometry of the scaffold: we present a solution to this problem for planar origami. Coaxial stacking of helices and entropic terms, particularly when loop closure exponents are taken to be larger than those for ideal chains, introduce interactions between staples. These cooperative interactions lead to the prediction of sharp assembly transitions with notable hysteresis that are consistent with experimental observations. We show that the model reproduces the experimentally observed consequences of reducing staple concentration, accelerated cooling and absent staples. We also present a simpler methodology that gives consistent results and can be used to study a wider range of systems including non-planar origami.

An experimental study of the putative mechanism of a synthetic autonomous rotary DNA nanomotor

“…These results are interesting in their own right because they suggest that it is possible to assemble a complex structure on the surface isothermally. It is likely that the staples cooperate during folding, because the binding of one staple will bring into closer proximity the binding sites for the next, which will then be able to bind more easily [25,26]. …”

Direct Simulation of the Self-Assembly of a Small DNA Origami

“…However, our results also show evidence for cooperativ-ity between staples in certain cases, which occurs when staples bring together distant parts of the scaffold strand, enhancing the geometry for other staples to bind their second domains. This inter-staple cooperativity, which has been incorporated in theoretical studies of origami assembly, 31 is particularly evident in the case of the four-way junction formed by the L and M staples.…”

“…30,31 Here, we are able to provide detailed microscopic insights and naturally capture the geometric and topological properties of the strands involved, but are much more restricted in time and length scales than the kinetic models. Furthermore, oxDNA can help parameterize the polymer modelling used in such domain-level models through detailed characterization of the thermodynamics of smaller model motifs.…”

“…Very recently, Dunn et al designed a "dimer" origami that had multiple fully-bonded states, and thus allowed folding pathways to be inferred from the assembly products. 30 The experimental work was complemented with a domain-level kinetic model 31 (which extended and improved upon previous such models 30,32 ) whose predictions were in good agreement with the experimental results, implying that the model predicted a realistic set of folding pathways.…”

Communication: Free energy of ligand-receptor systems forming multimeric complexes

“…Our results are exact in the limit of many linkers per particle. 21,22 We envisage applications of our theory to the association of more complex molecules like DNA tiles [23][24][25] or virial caspids. 26 In Sec.…”