SketchDNA: A GUI-Enabled Toolkit for Multiscale Modeling of Topological DNA Structures

Computational modeling tools have enabled detailed exploration of the structural dynamics of nucleic acids at the nanoscale. Despite these developments, a unified platform for creating multiscale models of topological DNA structures, which are of fundamental importance across rapidly converging biological disciplines, is lacking. Here we present a GUI-enabled topological DNA design tool, SketchDNA (SDNA), that facilitates a user-friendly and quick interface to create all-atom and coarse-grained models of DNA structures with tunable topological parameters. Building on the modular, open-source framework of SDNA, the software can be readily integrated with both emerging and existing DNA design platforms, such as oxDNA, mrDNA etc. We demonstrate the utility of SDNA computational framework by simulating conformational dynamics of three representative topological DNA structures, minicircles, catanenes, and Borromean rings. Analyzing the multiscale molecular dynamics (MD) simulation trajectories of these topological DNA systems, we characterize their equilibrium structure, fluctuations, and topological properties. The multiscale SDNA toolkit broadens the applications of MD simulations by enabling in-situ characterization of the biophysical properties of topological DNA nanostructures and is expected to serve as a valuable tool for the broader research community in molecular biophysics and DNA nanotechnology. SDNA is available as a free-to-use webserver at https://sdna.biotech.iith.ac.in while the source code is also available at GitHub repository.