oxDNA: coarse-grained simulations of nucleic acids made simple

Abstract

The fields of DNA and RNA nanotechnology have progressed from pioneering, proof-of-principle experiments to fully-fledged applications in material science, biology and medicine. These applications exploit the intrinsic programmability of nucleic acids to generate nano-and even micro-scale structures with tailored properties. However, the design of the DNA/RNA sequences that self-assemble into a desired structure is not straightforward and often relies on expensive trial-and-error experimental protocols. A complementary approach is provided by computer simulations, which can model biomacromolecules at different levels of detail, ranging from atomistic to continuous, and can be leveraged to investigate the whole range of time-and length-scales relevant for applications. Here we present oxDNA, a software package that has been designed to efficiently run coarse-grained simulations of DNA and RNA and also features an analysis suite aimed at post-processing the analysis of oxDNA/oxRNA trajectories. Statement of need The simulation of nucleic acids has become an important tool from the fundamental point of view to understand how these biomacromolecules behave and, from an application standpoint, to predict their behaviour under specific conditions (Dans et al., 2016). The ideal model for each specific problem, and therefore the level of detail with which DNA and RNA are to be described, depends on the time and length scales of interest: at one end of the spectrum there is quantum chemistry modelling, which can be used to probe the microscopic properties of a small number of nucleotides (Šponer et al., 2008), while at the other end there are continuum descriptions based on polymer theories such as the worm-like chain model (Nomidis et al., 2019) that can be used to study the behaviour of long DNA strands. A middle road is provided by coarse-grained models that describe nucleic acids at the nucleotide level (Doye et al., 2013). At this level of detail the oxDNA, oxDNA2 and oxRNA models has become popular choices to investigate the dynamics, thermodynamics and self-assembly behaviour of DNA and RNA systems (Sengar et al., 2021; Šulc et al., 2014), and have been used in more than a hundred publications to date. Functionality Here we present an updated version of the oxDNA code, an efficient, multi-technique simulation package written in C++ and specifically developed to carry out simulations of coarse-grained Poppleton et al. (2023). oxDNA: coarse-grained simulations of nucleic acids made simple. Journal of Open Source Software, 8(81), 4693. https://doi.org/10.21105/joss.04693.