Two-Phase Dynamics of DNA Supercoiling based on DNA Polymer Physics

TL;DR

This paper introduces a two-phase dynamic model for DNA supercoiling that captures key behaviors like plectoneme nucleation, diffusion, and hopping across multiple time scales with high computational efficiency.

Contribution

The authors developed a novel two-phase model based on DNA polymer physics that efficiently simulates DNA supercoiling dynamics across physiological time scales.

Findings

Model accurately reproduces supercoiling behaviors such as nucleation and hopping.

Two-phase model captures dynamics with minimal computational cost.

Results align well with detailed worm-like chain simulations.

Abstract

DNA supercoils are generated in genome regulation processes such as transcription and replication, and provide mechanical feedback to such processes. Under tension, DNA supercoil can present a coexistence state of plectonemic (P) and stretched (S) phases. Experiments have revealed the dynamic behaviors of plectoneme, e.g. diffusion, nucleation and hopping. To represent these dynamics with computational changes, we demonstrated first the fast dynamics on the DNA to reach torque equilibrium within the P and S phases, and then identified the two-phase boundaries as collective slow variables to describe the essential dynamics. According to the time scale separation demonstrated here, we accordingly developed a two-phase model on the dynamics of DNA supercoiling, which can capture physiologically relevant events across time scales of several orders of magnitudes. In this model, we systematically characterized the slow dynamics between the two phases, and compared the numerical results with that from the DNA polymer physics-based worm-like chain model. The supercoiling dynamics, including the nucleation, diffusion, and hopping of plectoneme, have been well represented and reproduced, using the two-phase dynamic model, at trivial computational costs. Our current developments, therefore, can be implemented to explore multi-scale physical mechanisms of the DNA supercoiling-dependent physiological processes.