Structure and conformational dynamics of scaffolded DNA origami nanoparticles

Abstract

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 5–100 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 and mechanical properties of DX-based assemblies that are inaccessible to all-atom based models alone.

Investigating the sequence-dependent mechanical properties of DNA nicks for applications in twisted DNA nanostructure design

“…We performed MD simulations to investigate the conformational dynamics of the DNA double helices using a freely available program, NAMD (50) with the CHARMM36 force field (51) for nucleic acids. The CHARMM36 force field was adopted since it showed general agreements with experiments from the previous MD studies of DNA nanostructures (4–6,16,17). Each DNA oligomer was explicitly solvated in a 60 Å × 60 Å × 180 Å cubic TIP3P water box (52).…”

DNA nanostructures coordinate gene silencing in mature plants

“…Supplementary Video S1. Mechanical stiffness calculations quantify the root mean square fluctuations (RMSF) of HT the monomer nanostructure simulated by CanDo (3,4). White and red represent low and high relative flexibility, respectively.…”

DNA Nanostructures Coordinate Gene Silencing in Mature Plants

“…In comparing the HT monomer to the nanostring, we find that a higher nanostructure stiffness (0.83 vs. 1 x 10 -4 kb nanostructure /kb dsDNA for the HT monomer versus nanostring, respectively) results in higher cellular uptake (59.5 ± 1.5 % vs. 35.8 ± 0.9 % ; mean ± SD for the monomer versus nanostring, respectively). We also simulated the flexibility of siRNA alone, HT, and nanostring DNA nanostructures using CanDo (35,36) (supplementary methods) to understand how nanostructure stiffness affects plant cell internalization. Mechanical stiffness calculations quantifying the root mean square fluctuations (RMSF), as summarized in Figure S7, demonstrate that the nanostring is significantly more flexible than the HT monomer (supplementary video 1 and 2).…”