Natarajan, A. K. | bioRxiv Science

bioRxiv2026

AutoMod: A Software Tool for High-Accuracy Design of Curved DNA Origami Nanostructures

In the design of DNA origami (DO) nanostructures, structural information, such as equilibrium conformation, is encoded by nucleotide sequences. The problem of finding the correct sequences for a certain target conformation is a demanding computational task, commonly addressed with the help of computer-aided design software. However, strongly curved structures where DNA helices span non-closed routes have remained extremely challenging to realize. Here, we present AutoMod, a software tool that attains significantly increased correspondence of an ideal target shape with the semi-automatically generated design. Dissimilarity of a target with a design is measured with root mean square deviation between simplified point set representations of the target shape and the computationally predicted equilibrium conformation of a design. Compared to previous methods, statistically significant decreases in mean root mean square deviation are observed with all tested target shapes. A benchmark DO structure, designed with AutoMod, is realized experimentally and its conformation is resolved with single-particle reconstruction. Subsequently, high agreement with computational results is observed. We anticipate improvements in design accuracy to facilitate the successful application of DO nanostructures in fields such as nanofabrication, biomedical engineering, and biosensing.

bioengineering↗

bioRxiv2022

Algorithmic design of 3D wireframe RNA polyhedra

We address the problem of de novo design and synthesis of nucleic acid nanostructures, a challenge that has been considered in the area of DNA nanotechnology since the 1980s and more recently in the area of RNA nanotechnology. Towards this goal, we introduce a general algorithmic design process and software pipeline for rendering 3D wireframe polyhedral nanostructures in single-stranded RNA. To initiate the pipeline, the user creates a model of the desired polyhedron using standard 3D graphic design software. As its output, the pipeline produces an RNA nucleotide sequence whose corresponding RNA primary structure can be transcribed from a DNA template and folded in the laboratory. As case examples, we design and characterize experimentally three 3D RNA nanostructures: a tetrahedron, a bipyramid and a prism. The design software is openly available, and also provides an export of the targeted 3D structure into the oxRNA molecular dynamics simulator for easy simulation and visualization.

bioengineering↗