A Primer on the oxDNA Model of DNA: When to Use it, How to Simulate it and How to Interpret the Results

Abstract

The oxDNA model of Deoxyribonucleic acid has been applied widely to systems in biology, biophysics and nanotechnology. It is currently available via two independent open source packages. Here we present a set of clearly documented exemplar simulations that simultaneously provide both an introduction to simulating the model, and a review of the model’s fundamental properties. We outline how simulation results can be interpreted in terms of—and feed into our understanding of—less detailed models that operate at larger length scales, and provide guidance on whether simulating a system with oxDNA is worthwhile.

OxDNA to study species interactions

“…• a p4 and a resource • a p10 and a resource • two p4 strands • two p10 strands • a p4 and a p10 • a p4, a p10 and a resource These small, controlled setups, allowed us to focus on the details of two-strands (predatorprey or predator-predator) and three-strands (2 predators -prey) interactions. For each of these cases, we run n independent Molecular Dynamics simulations with the oxDNA package [25][26][27], following the protocol outlined in the Methods. In particular, all the systems were studied over n = 10 statistically independent simulations, while the system with three strands has been simulated n = 20 times.…”

“…The Molecular Dynamics simulations described in this work are all performed using the oxDNA software [25][26][27]; in the simulations of the larger systems described here, GPU backend has been exploited [32]. In particular, the more refined oxDNA-2 coarse-grained model is employed in all this work, to better mimic the solvent effect and include more realistic details into the simulations [26].…”

“…ssDNA oligomers are chains of unpaired nucleotides, highly flexible, markedly different from their much stiffer doublestranded counterpart. The great advantage of such a choice lies in the possibility to combine the knowledge of the polymer with the conceptual simplicity of the interactions among DNA filaments, aided by the large number of tools available from both the experimental [22][23][24] and computational [25][26][27] points of view. ssDNA oligomers are made by combinations of four building blocks (the nucleotides A/C/T/G) which can canonically bind in a selective way: A/T, C/G.…”

“…From the theoretical and computational perspective, the oxDNA coarse-grained model [25][26][27]30] provides us with a formidable magnifying glass to explore the physical processes driving to hybridization between two strands [31]. The oxDNA force field is a model of DNA at the nucleotide level, which embodies pairwise-additive forces due to the excluded volume, the phosphate backbone connectivity, the stacking, cross-stacking and coaxial stacking and hydrogen bonding between complementary base pairs [30].…”

Weak tension accelerates hybridization and dehybridization of short oligonucleotides

“…Using Equation 3, we calculated an average k on value of 2.3 s −1 µM −1 (where the probe concentration was estimated using the [10.2 nm] 3 simulation box volume) and an average k off value of 9.9 min −1 . A direct comparison between the calculated rates and the measured rates is not accurate considering that coarse-graining is known to speed up dynamical timescales by smoothing energy landscapes and neglecting hydrodynamic effects [73-75]. Nonetheless, the reaction paths should shed light on the nature of the transition states.…”