A Single Nucleotide Resolution Model for Large-Scale Simulations of Double Stranded DNA

Abstract

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.

Complexation of single stranded RNA with an ionizable lipid: an all-atom molecular dynamics simulation study

“…An alternative approach, which is based on a simplified description of molecules, is the coarsegrained models. 45,46 These models can provide information at longer length and time scales and can sufficiently describe large-scale motions, mechanical properties, native structures and thermodynamics. Various coarse-grained models have been used for RNA molecules, 36 with the MARTINI scheme being widely used.…”

Mechanistic modeling of chromatin folding to understand function

“…"Mechanistic" models are used to test hypothesis on underlying mechanisms; and "inverse" models, where data are used to, e.g., infer chromatin structures consistent with these.These often involve CG models of DNA which resolve the DNA double strands and superhelical structure, e.g., the oxDNA model 17 , or three-spheres-per-nucleotide (3SPN) model52 . These can be used to study supercoiling14 , DNA melting, and DNA-protein interactions. Larger systems can be treated using simpler models which track twist deformations without resolving individual DNA strands53 .Detailed CG models based on nucleosome crystal structures can be used to simulate small fibres18,54 .Simplified models representing nucleosomes as disks or spheres have been used to simulate, e.g.…”

Structural and Linear Elastic Properties of DNA Hydrogels by Coarse-Grained Simulation

“…Furthermore, our model is computationally efficient compared to current DNA simulation models [30][31][32] as we neglect the binding specificity using a patch interactions with given interaction strength. This is preferable for predicting the structural and dynamic properties of larger scale DNA self-assembly systems with repeating building blocks, which is normally very costly if the per-nucleotide interaction is considered.…”

“…With regard to DNA hydrogels, our interest lies in the structure and mechanics of largescale systems, hence base-pair models 19,[30][31][32] are too detailed. Computational models of DNA gels self-assembled from branched DNA complexes have been proposed to mimic the bulk behaviour of the system, particularly focusing on the assembly and gelation processes.…”