A Simple and Fast Semiautomatic Procedure for the Atomistic Modeling of Complex DNA Polyhedra

Abstract

A semiautomatic procedure to build complex atomistic covalently linked DNA nanocages has been implemented in a user-friendly, free, and fast program. As a test set, seven different truncated DNA polyhedra, composed by B-DNA double helices connected through short single-stranded linkers, have been generated. The atomistic structures, including a tetrahedron, a cube, an octahedron, a dodecahedron, a triangular prism, a pentagonal prism, and a hexagonal prism, have been probed through classical molecular dynamics and analyzed to evaluate their structural and dynamical properties and to highlight possible building faults. The analysis of the simulated trajectories also allows us to investigate the role of the different geometries in defining nanocages stability and flexibility. The data indicate that the cages are stable and that their structural and dynamical parameters measured along the trajectories are slightly affected by the different geometries. These results demonstrate that the constraints imposed by the covalent links induce an almost identical conformational variability independently of the three-dimensional geometry and that the program presented here is a reliable and valid tool to engineer DNA nanostructures.

In Silico and In Cell Analysis of Openable DNA Nanocages for miRNA Silencing

“…The H4 DNA nanocage (H4-NC) was designed by starting from a truncated octahedral DNA cage structure [24], composed by eight different oligonucleotides, extensively characterized by our group [11,12,[18][19][20]22]. The DNA cage structure is covalently closed and composed of 12 double-stranded B-DNA helices ( Figure 1A), forming the edges of the structure, connected by short single-stranded thymidine linkers constituting square truncated faces ( Figure 1B).…”

“…The scaffold of the octahedral DNA nanocage was built with Polygen software (https://portal.if. usp.br/gfcx/pt-br/node/345, accessed on 12/10/2019) [20], using oligonucleotides sequences previously designed to experimentally assemble truncated octahedral geometries [24]. The sequences of the DNA hairpins and of the oligonucleotides acting as allosteric remodelers were designed and optimized through a thermodynamic approach, using NUPACK (http://nupack.org/, accessed on 12/10/2019) [28].…”

“…DNA nanostructures have also been functionalized to selectively interact with intracellular miRNA, mainly to detect their concentration, using electrochemical current or fluorescence signals [15][16][17]. Here, taking advantage of our experience matured in the last years in the characterization of different types of fully covalently octahedral DNA nanocages [11,12,[18][19][20][21], including their receptor-mediated cell targeting and their efficacy in selective drug delivery [5,22,23], we propose a new nanostructure for a possible therapeutic use as an efficient captor of the oncogenic miR21. For this purpose, we have initially engineered in one face of a truncated DNA cage four DNA hairpins complementary to a specific oligonucleotide (Fuel), to form a nanocage (H4-NC) with selective oligonucleotide sequestering activity.…”

Selective targeting and degradation of doxorubicin-loaded folate-functionalized DNA nanocages

“…2,3,4 During the last years our group has in vitro and in silico characterized various types of fully covalently bound truncated octahedral DNA nanocages and studied their behaviour in cells. [5][6][7][8][9][10] DNA nanocages, including octahedral cages, possess many attractive properties for cancer nanotherapy: they are intrinsically nontoxic, with excellent biocompatibility and biodegradability, [11][12][13] are readily internalized by living cells via endocytosis, 10,14 show high resistance to degradation 15,16 and can efficiently intercalate anticancer drugs such as doxorubicin. [17][18][19][20] Doxorubicin (Dox) is one of the most commonly used anticancer agents for the treatment of a wide variety of solid tumours including breast, ovarian, prostate, brain, cervix and lung cancers and haematological malignancies, such as multiple myeloma, several types of leukaemia and lymphomas.…”

Intrinsic Dynamics Analysis of a DNA Octahedron by Elastic Network Model

“…Mathematical models based on knot and topological graph theory have been built to unravel the basic structural rules driving the assembly of these nanostructures and design the DNA nanocages topologies [ 22 , 23 , 24 , 25 , 26 ]. A computational program called Polygen has also been developed to easily engineer DNA nanocages [ 27 ].…”