Conformational dynamics and mechanical properties of biomimetic RNA, DNA, and RNA-DNA hybrid nanotubes: an atomistic molecular dynamics study

With the nanotechnology boom, artificially designed nucleic acid nanotubes have aroused interest due to their practical applications in nanorobotics, vaccine design, membrane channels, drug delivery, and force sensing. In this paper, computational study was performed to investigate the structural dynamics and mechanical properties of RNA nanotubes (RNTs), DNA nanotubes (DNTs), and RNA-DNA hybrid nanotubes (RDHNTs). So far, the structural and mechanical properties of RDHNTs have not been examined in experiments or theoretical calculations, and there is limited knowledge regarding these properties for RNTs. Here, the simulations were carried out using the equilibrium molecular dynamics (MD) and steered molecular dynamics (SMD) approaches. Using in-house scripting, we modeled hexagonal nanotubes composed of six double-stranded molecules connected by four-way Holliday junctions. Classical MD analyses were performed on the collected trajectory data to investigate structural properties. Analyses of the microscopic structural parameters of RDHNT indicated a structural transition from the A-form to a conformation between the A- and B-forms, which may be attributable to the increased rigidity of RNA scaffolds compared to DNA staples. Comprehensive research on the elastic mechanical properties was also conducted based on spontaneous thermal fluctuations of nanotubes and employing the equipartition theorem. The Young's modulus of RDHNT (E = 165 MPa) and RNT (E = 144 MPa) was found to be almost the same and nearly half of that found for DNT (E = 325 MPa). Furthermore, the results showed that RNT was more resistant to bending, torsional, and volumetric deformations than DNT and RDHNT. We also used non-equilibrium SMD simulations to acquire comprehensive knowledge of the mechanical response of nanotubes to tensile stress.