During the last decade coarse-grained nucleotide models have emerged that allow us to study DNA and RNA on unprecedented time and length scales. Among them is oxDNA, a coarse-grained, sequence-specific model that captures the hybridisation transition of DNA and many structural properties of single- and double-stranded DNA. oxDNA was previously only available as standalone software, but has now been implemented into the popular LAMMPS molecular dynamics code. This article describes the new implementation and analyses its parallel performance. Practical applications are presented that focus on single-stranded DNA, an area of research which has been so far under-investigated. The LAMMPS implementation of oxDNA lowers the entry barrier for using the oxDNA model significantly, facilitates future code development and interfacing with existing LAMMPS functionality as well as other coarse-grained and atomistic DNA models.

The computational modelling of DNA is becoming crucial in light of new advances in DNA nanotechnology, single-molecule experiments and in vivo DNA tampering. Here we present a mesoscopic model for double stranded DNA (dsDNA) at the single nucleotide level which retains the characteristic helical structure, while being able to simulate large molecules -up to a million base pairs -for timescales which are relevant to physiological processes. This is made possible by an efficient and highlyparallelised implementation of the model which we discuss here. We compare the behaviour of our model with single molecule experiments where dsDNA is manipulated by external forces or torques. We also present some results on the kinetics of denaturation of linear DNA.

There is a long-standing experimental observation that the melting of topologically constrained DNA, such as circular-closed plasmids, is less abrupt than that of linear molecules. This finding points to an intriguing role of topology in the physics of DNA denaturation, which is however poorly understood. Here, we shed light on this issue by combining large-scale Brownian Dynamics simulations with an analytically solvable phenomenological Landau mean field theory. We find that the competition between melting and supercoiling leads to phase coexistence of denatured and intact phases at the single molecule level. This coexistence occurs in a wide temperature range, thereby accounting for the broadening of the transition. Finally, our simulations show an intriguing topology-dependent scaling law governing the growth of denaturation bubbles in supercoiled plasmids, which can be understood within the proposed mean field theory.One of the most fascinating aspects of DNA is that its biological function is intimately linked to its local topology [1]. For instance, DNA looping [2,3] and supercoiling [1,4,5] are well-known regulators of gene expression, and a variety of proteins, such as Polymerases, Gyrases and Topoisomerases, can affect genomic function by acting on DNA topology [1,2].Fundamental biological processes such as DNA transcription and replication are associated with local opening of the double helix, a phenomenon that can be triggered in vitro by varying temperature, pH or salt concentration [6]. The melting transition of DNA from one double-stranded (ds) helix to two single-stranded (ss) coils has been intensively studied in the past by means of buoyant densities experiments [7], hyperchromicity spectra [8], AFM measurements [9], singlemolecule experiments [10] and fluorescence microscopy [11].In particular, experiments [6,7] and theories [12,13] have shown that the "helix-coil" transition in linear or nicked DNA molecules, which do not conserve the total linking number between the two strands, is abrupt and bears the signature of a first-order-like transition. On the other hand, the same transition is much smoother for DNA segments whose linking number is topologically preserved, such as circular, covalently-closed ones [7,14].Understanding the physical principles underlying DNA melting in topologically constrained (tc) DNA is important since this is the relevant scenario in vivo. For instance, bacterial DNA is circular, while in eukaryotes DNA wraps around histones [2], and specialised proteins are able to inhibit the diffusion of torsional stress [15].Intriguingly, and in stark contrast with the behaviour of linear, or topologically free (tf), DNA, the width of the melting transition of tcDNA is relatively insensitive to the precise nucleotide sequence [14] thereby suggesting that a universal physical mechanism, rather than biochemical details, may underlie the aforementioned broadening. While biophysical theories of tcDNA melting do exist, they do not reach a consensus as to whether the transition shoul...

We study the effect of transcription on the kinetics of DNA supercoiling in three dimensions by means of Brownian dynamics simulations of a single-nucleotide–resolution coarse-grained model for double-stranded DNA. By explicitly accounting for the action of a transcribing RNA polymerase (RNAP), we characterize the geometry and nonequilibrium dynamics of the ensuing twin supercoiling domains. Contrary to the typical textbook picture, we find that the generation of twist by RNAP results in the formation of plectonemes (writhed DNA) some distance away. We further demonstrate that this translates into an “action at a distance” on DNA-binding proteins; for instance, positive supercoils downstream of an elongating RNAP destabilize nucleosomes long before the transcriptional machinery reaches the histone octamer. We also analyze the relaxation dynamics of supercoiled double-stranded DNA, and characterize the widely different timescales of twist diffusion, which is a simple and fast process, and writhe relaxation, which is much slower and entails multiple steps.

The computational modelling of DNA is becoming crucial in light of new advances in DNA nano-technology, single-molecule experiments and in vivo DNA tampering. Here we present a mesoscopic model for double stranded DNA (dsDNA) at the single nucleotide level which retains the characteristic helical structure, while being able to simulate large molecules - up to a million base pairs - for time-scales which are relevant to physiological processes. This is made possible by an efficient and highly-parallelised implementation of the model which we discuss here. The model captures the main characteristics of DNA, such as the different persistence lengths for double and single strands, pitch, torsional rigidity and the presence of major and minor grooves. The model constitutes a starting point for the future implementation of further features, such as sequence specificity and electrostatic repulsion. We show that the behaviour of the presented model compares favourably with single molecule experiments where dsDNA is manipulated by external forces or torques. We finally present some results on the kinetics of denaturation of linear DNA and supercoiling of closed dsDNA molecules.