Deciphering the Structural Properties That Confer Stability to a DNA Nanocage

Abstract

A DNA nanocage has been recently characterized by small-angle X-ray scattering (SAXS) and cryo-transmission electron microscopy as a DNA octahedron having a central cavity larger than the apertures in the surrounding DNA lattice. Starting from the SAXS data, a DNA nanocage has been modeled and simulated by classical molecular dynamics to evaluate in silico its structural properties and stability. Global properties, principal component analysis, and DNA geometrical parameters, calculated along the entire trajectory, indicate that the cage is stable and that the B-DNA conformation, also if slightly distorted, is maintained for all the simulation time. Starting from the initial model, the nanocage scaffold undergoes a contraction of the thymidine strands, connecting the DNA double helices, suggesting that the length of the thymidine strands is a crucial aspect in the modulation of the nanocage stability. A comparison of the average structure as obtained from the simulation shows good agreement with the SAXS experimental data.

Influence of the single‐strand linker composition on the structural/dynamical properties of a truncated octahedral DNA nano‐cage family

“…The global RMSF values, although displaying a more complex behavior, show a comparable sinusoidal trend triggered by the contribution of the previously described cage rotational motion . These data indicate that the linker's composition does not significantly alter the dynamical properties of the three cages.…”

“…The three nano‐cages have been built starting from the initial model proposed by Falconi et al, manually adding the 24 seven thymidine, adenine, and A/T mixed linkers to the cage structure using the SYBYL 6.0 suite (TRIPOS, http://www.tripos.com), to obtain the nano7T, the nano7A, and the nano7AT final structures, respectively. The clashes between the double helices and the single‐stranded linkers have been removed through the SYBYL Anneal module and then a first minimization of the entire structure has been performed using the SYBYL Maximin2 module.…”

“…Thus, atomistic simulations, able to predict the structural/dynamical properties of nanostructures before experiments, can give useful information concerning the stability of the assembly obtained starting from the predesigned sequences. During the past few years molecular dynamics (MD) atomistic simulations have been successfully used to characterize the structure and the dynamics of Seeman DNA nanostructures, to investigate the properties of a truncated octahedral DNA nano‐cage family, to probe the stability and the dynamical properties of DNA nanocircles, supercoiled DNA structures, or human telomeric G‐quadruplex loops and to investigate the temperature dependent encapsulation mechanism of a DNA nanostructure …”

Visualization of bionanostructures using transmission electron microscopical techniques

“…Moreover, nanomedicine has been suggested as a major field of application of nanotechnological developments. In particular, nanotechnology offers promising possibilities as diagnostic tool (Caldorera‐Moore and Peppas,2009; Canelas et al,2009; Davis et al,2009; Godin et al,2010), for tissue engineering (Caldorera‐Moore and Peppas,2009; Webber et al,2010) as well as drug delivery (Caldorera‐Moore and Peppas,2009; Canelas et al,2009; Christie et al,2010; Davis et al,2009; Farokhzad and Langer,2009; Godin et al,2010; Huynh et al,2009; Malam et al,2009; Masotti and Ortaggi,2009; Modi et al,2010).…”

The Potential of Nucleic Acid-Based Nanoparticles for Biomedical Application

“…The geometry is highly stable and its conformational variability is modulated by the length of the single stranded linker, being larger for longer linkers. [26][27][28][29] Fig. 1.…”