Synthetic DNA is a highly programmable nanoscale material that can be designed to self-assemble into 3D structures that are fully determined by underlying Watson-Crick base pairing. The double crossover (DX) design motif has demonstrated versatility in synthesizing arbitrary DNA nanoparticles on the 5100 nm scale for diverse applications in biotechnology. Prior computational investigations of these assemblies include all-atom and coarse-grained modeling, but modeling their conformational dynamics remains challenging due to their long relaxation times and associated computational cost. We apply all-atom molecular dynamics and coarse-grained finite element modeling to DX-based nanoparticles to elucidate their fine-scale and global conformational structure and dynamics. We use our coarse-grained model with a set of secondary structural motifs to predict the equilibrium solution structures of 45 DX-based DNA origami nanoparticles including a tetrahedron, octahedron, icosahedron, cuboctahedron and reinforced cube. Coarse-grained models are compared with 3D cryo-electron microscopy density maps for these five DNA nanoparticles and with all-atom molecular dynamics simulations for the tetrahedron and octahedron. Our results elucidate non-intuitive atomic-level structural details of DX-based DNA nanoparticles, and offer a general framework for efficient computational prediction of global and local structural andmechanical properties of DX-based assemblies that are inaccessible to all-atom based models alone.
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