Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Jun 20;45(11):6284-6298.
doi: 10.1093/nar/gkx378.

Structure and Conformational Dynamics of Scaffolded DNA Origami Nanoparticles

Affiliations
Free PMC article

Structure and Conformational Dynamics of Scaffolded DNA Origami Nanoparticles

Keyao Pan et al. Nucleic Acids Res. .
Free PMC article

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.

Figures

Figure 1.
Figure 1.
Mechanical models of secondary structural motifs of programmed DNA assemblies considered in this work. (A) Each base pair in the secondary structure of a programmed DNA assembly (left) is modeled as a FE node represented as a blue sphere located at formula image with three reference axes formula image, formula image and formula image (center). There is a one-to-one correspondence between the reference frame formula image and the all-atom model of the same base pair (center). Thus, the FE model can be represented by an all-atom model (right). The arbitrarily chosen strand, to which axis formula image points to, is colored in blue, and the other strand is in gray. (B) A set of secondary structural motifs (top) and the corresponding FE models (bottom) in programmed DNA assemblies. Nucleotides and the FE model in a given motif are colored in red, while those in the flanking base pairs are colored in gray. A global reference coordinate system formula image is defined for the FE models of double crossovers, single crossovers, open nicks, and bulges. The mechanical model for a double crossover and that for a single crossover each contain two torsional springs: one connects nodes formula image and formula image, and the other one connects nodes formula image and formula image. Base pair n1n2 stacks with base pair n3n4 in a nick but not in an open nick. (C) (Left) FE and the corresponding all-atom model, rendered in ribbons, of a bulge between nodes formula image and formula image. The 5΄-end and the 3΄-end of the blue strand are marked. In addition, the reference axes x, y and z are defined as the reference axes formula image, formula image, and formula image of node formula image. (Center) Two probability distributions of the two rotation angles formula image and formula image about axes x and z, respectively, computed from all-atom MD simulations. A Gaussian is fitted to each distribution. Means of the fitted Gaussians are plotted as vertical dashed lines. (Right) The autocorrelation functions (ACFs) of formula image and formula image from all-atom MD simulations. A single exponential is fitted to each ACF. The inset shows four snapshots sampled at 200, 400, 600, and 800 ns in the MD trajectory of the bulge. These snapshots are aligned with each other.
Figure 2.
Figure 2.
Mechanical models of unconstrained multi-arm vertices. (A) Secondary structures (top) and corresponding FE models at the ground-state mechanical free energy (bottom) of 3-arm, 4-arm, 5-arm, and 6-arm vertices consisting of duplexes, double crossovers, single crossovers, and bulges. An N-arm vertex contains N ssDNA regions, each of which comprises five unpaired thymine bases. As an example, one of the three ssDNA regions in the 3-way vertex is encircled by red dots. The secondary structure and the first orthogonal view of each vertex are oriented such that the minor grooves of DNA at the center of the vertex face the reader. The FE models are represented as all-atom models with DNA stranded colored in the same way as in the secondary structures. All scale bars are 5 nm. (B) (Top) Four aligned snapshot sampled at 100, 200, 300, and 400 ns in the MD trajectory of the 3-arm junction. (Bottom) Four aligned snapshot sampled at 100, 200, 300, and 400 ns in the MD trajectory of the 4-arm junction. (C) Histogram of various geometric values calculated from MD trajectories. Duplex bend-angles in degrees (top left), duplex torsional twist-angles in degrees (top right), out-of-plane bend-angles in degrees (bottom left), and radial vacancies in angstroms (bottom right) during 500-ns (3-arm junction, 4-arm junction) and 1-μs (duplex bulge) MD simulations. Solid lines indicate the mean value during the MD trajectory and dashed lines indicate the value obtained from the ground-state FE model.
Figure 3.
Figure 3.
Equilibrium structures of the polyhedral nanoparticles generated by the FE framework and the MD simulations. (A) Four aligned snapshots at 25, 50, 75, and 100 ns of the MD trajectory of the tetrahedron. (B) The snapshot at 25 ns of the tetrahedron with vertices with the absence and presence of interactions between unpaired bases termed as ‘open vertices’ and ‘closed vertices’, respectively. (C) Four snapshots at 25, 50, 75, and 100 ns of the MD trajectory of the octahedron are rendered in the same way as in (a). (D) The snapshot at 25 ns of the octahedron. (E) The distribution of the twist-angle, bow-angle, and radial vacancy during the MD simulations of the tetrahedral and octahedral nanoparticles. Each angle is averaged over the four vertices of the tetrahedron or the six vertices of the octahedron. Solid lines indicate the mean value during the MD trajectory and dashed lines indicate the value obtained from the ground-state FE model. (F–J) FE equilibrium structures, colored in blue, of (F) the tetrahedron, (G) the octahedron, (H) the icosahedron, (I) the cuboctahedron, and (J) the reinforced cube were fit into the reconstructed cryo-EM map using the software UCSF Chimera (91). All scale bars are 5 nm.
Figure 4.
Figure 4.
Equilibrium structures generated by the FE framework compared to the geometric model. (A) Equilibrium structures of the 45 polyhedral nanoparticles presented in a recent study (11). The nanoparticles consist of five Platonic solids (blue), 10 Archimedean solids (red), 10 Johnson solids (green), 10 Catalan solids (orange), and 10 polyhedra with miscellaneous shapes (purple). The geometric shapes of these structures are listed in Table 2. (B) Zoom-ins of the octahedron, cuboctahedron, gyroelongated square bipyramid, and rhombic dodecahedron (left to right, boxed in dashed lines in A) highlight similarities between the recent study and the current work, indicated by small RMSD values. (C) Zoom-ins of the Goldberg polyhedron, double helix, nested cube, and double torus (left to right, boxed in solid lines in A) highlight differences between the two works, indicated by large RMSD values.

Similar articles

See all similar articles

Cited by 5 articles

References

    1. Seeman N.C. Nucleic acid junctions and lattices. J. Theor. Biol. 1982; 99:237–247. - PubMed
    1. Seeman N.C. Nanomaterials based on DNA. Annu. Rev. Biochem. 2010; 79:65–87. - PMC - PubMed
    1. Wang P., Gaitanaros S., Lee S., Bathe M., Shih W.M., Ke W. Programming self-assembly of DNA origami honeycomb two-dimensional lattices and plasmonic metamaterials. J. Am. Chem. Soc. 2016; 138:7733–7740. - PubMed
    1. Rothemund P.W.K. Folding DNA to create nanoscale shapes and patterns. Nature. 2006; 440:297–302. - PubMed
    1. Castro C.E., Kilchherr F., Kim D.N., Shiao E.L., Wauer T., Wortmann P., Bathe M., Dietz H. A primer to scaffolded DNA origami. Nat. Methods. 2011; 8:221–229. - PubMed
Feedback