Thermodynamics and Kinetics of Blunt-End Driven DNA Origami Tiles Dimerization through Coarse-Grained Molecular Dynamics Simulations

Directed self-assembly of DNA origami structures offers a powerful way to create complex devices at the nanoscale, with promising applications in a broad range of fields such as biosensing, nanoscale robotics, photonics, computing, and drug delivery. However, the complexity of these structures obscures the fundamental principles of their assembly process. To unveil such principles, we developed a coarse-grained model for DNA origami structures which allows for kinetic and thermodynamic predictions of blunt end driven dimerization. The simplicity of this model, which accurately captures multiple features observed in experiments, allows us to characterize how the geometric, elastic, and energetic properties of the blunt end motifs modify the enthalpy and entropy of dimerization, and highlights the role of entropic effects in the previously reported (albeit not fully understood) sub-linearity of the free energy of dimerization with respect to the number of active binding sites. This model also allows us to predict the effects of cytosine methylation and DNA mismatches on binding energy, enabling tunable molecular recognition with many potential uses in nanotechnology.