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

Abstract

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.