Supercoiling and local denaturation of plasmids with a minimalist DNA model.

TLDR: A new one-bead-per-nucleotide coarse-grained model that combines structural accuracy and predictive power, achieved by means of the accurate choice of the force field terms and their unbiased statistically based parametrization is reported.

Abstract: We report molecular dynamics simulations of DNA nanocircles and submicrometer-sized plasmids with torsional stress. The multiple microseconds time scale is reached thanks to a new one-bead-per-nucleotide coarse-grained model that combines structural accuracy and predictive power, achieved by means of the accurate choice of the force field terms and their unbiased statistically based parametrization. The model is validated with experimental structural data and available all-atom simulations of DNA nanocircles. Besides reproducing the nanocircles' structures and behavior on the short time scale, our model is capable of exploring three orders of magnitude further in time and to sample more efficiently the configuration space, unraveling novel behaviors. We explored the microsecond dynamics of entire small plasmids and observed supercoiling and compaction in the overtwisted case. The stability of overtwisted nanocircles and plasmids is predicted up to macroscopic time scales. Conversely, in the undertwisted case, at physiological values of the superhelical density, after a metastable phase of supercoiling-compaction, we observe the formation and the complex dynamics of denaturation bubbles over a multiple microseconds time scale. Our results indicate that the torsional stress is involved in a delicate balance with the temperature to determine the denaturation equilibrium and regulate the transcription process.