Evolutionary Refinement of DNA Nanostructures Using Coarse-Grained Molecular Dynamics Simulations

In the past decade, DNA nanostructures have made the leap from small assemblies of a handful of oligonucleotides to megadalton objects assembled from hundreds or thousands of component DNA strands. Most DNA designs today are either lattice based with simple and reliable design tools or lattice free with a larger shape space but more challenging design and lower rigidity. In parallel with the development of DNA nanostructures, software packages for the simulation of nucleic acids have seen rapid development allowing for the simulation of the dynamics of full DNA nanostructure assemblies. Here, we implement an unsupervised software based on the coarse-grained molecular dynamics package oxDNA to simulate DNA origami structures and evaluate their rigidity. From this, the software autonomously produces mutant structures by adding or removing base pairs or modifying the positions of internal supports. These mutant structures are iteratively generated and evaluated by simulation to create an in silico evolution toward more rigid DNA nanostructures.