Construction of Foldback Intercoil DNA Nanostructures and Analysis of Their Vibrational Modes

Abstract

A foldback intercoil (FBI) DNA nanostructure has important biological functions that are closely related to specific life phenomena, and it has a geometrically unique fourstranded DNA configuration that consists of two folded-back antiparallel DNA double helixes intertwining in the major groove by sharing the same helix axis. However, the geometrical complexity of its unusual FBI configuration has prohibited its in vitro formation from direct contact between B-form DNA duplexes. Although several efforts have been made to investigate its functionalities and configurations, the FBI structures have been rarely constructed (via structural DNA nanotechnology) and simulated (through computational biology) to determine their geometrical stability, experimental validity, and engineering feasibility. In this study, we designed an FBI configuration with a homologous DNA base sequence implemented on either a double-crossover DNA tile or a double-crossover DNA lattice which was observed using an atomic force microscope. In addition, we propose a 3-dimensional FBI structural model and perform a normal-mode analysis based on the mass-weighted chemical elastic network model. These results provide an implementation of a biological simulation in the design of unusual DNA nanostructures, a prediction of their corresponding biological functionality, and an assessment of the feasibility to construct naturally existing biological configurations through synthetic DNA molecules.

A computational model for structural dynamics and reconfiguration of DNA assemblies

“…9 ). The estimated breathing frequency was 2.35 GHz, which was lower than the structural vibrations observed in small DNA motifs (16 to 150 base-pairs) with 300 to 600 GHz 31 , 32 (Supplementary Table 4 ). This breathing motion could be predicted using the normal mode analysis (NMA) in a vacuum as well, but an unreasonably small frequency of 1.83 MHz was predicted (Fig.…”

Fabrication and Characterization of Finite-Size DNA 2D Ring and 3D Buckyball Structures

“…In an elastic network model (ENM), representative atoms are modeled as unit point masses, and connectivity between atoms is represented as a unit spring constant that varies depending on the cutoff distance, which is usually 12 Å in a C α coarse-grained protein model [ 34 , 35 , 36 , 37 , 38 ]. ENM methodology has been mainly used to analyze intrinsic mode shapes of proteins, but recently, it has also been used to analyze intrinsic vibrational features of DNA/RNA structures because of its advantages (i.e., low computational cost and large conformational change prediction) compared to the traditional full-atom molecular dynamics (MD) simulations [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ]. In comparison with a traditional ENM, the MWCENM is a more precise modeling method because it considers both the inertia effect and the chemical bond information of the target system.…”

“…There have been considerable efforts to analyze vibrational characteristics based on NMA for various DNA/RNA native structures [ 22 , 23 , 24 , 25 , 26 ]. Although dynamic analysis for some fabricated nanostructures has also been performed by NMA [ 20 , 21 , 27 , 28 , 29 , 30 , 31 ], finite-size nanostructures that have more complex geometries, as well as larger molecular weights, have rarely been studied.…”