Complex Systems Division, Beijing Computational Science Research Center, Beijing, China.
Department of Physics and Astronomy, Department of Chemistry, NSF-Simons Center for Multiscale Cell Fate Research, University of California, Irvine, California.
Biophys J. 2022 Feb 15;121(4):658-669. doi: 10.1016/j.bpj.2022.01.001. Epub 2022 Jan 10.
DNA supercoils are generated in genome regulation processes such as transcription and replication and provide mechanical feedback to such processes. Under tension, a DNA supercoil can present a coexistence state of plectonemic and stretched phases. Experiments have revealed the dynamic behaviors of plectonemes, e.g., diffusion, nucleation, and hopping. To represent these dynamics with conformational changes, we demonstrated first the fast dynamics on the DNA to reach torque equilibrium within the plectonemic and stretched phases, and then identified the two-phase boundaries as collective slow variables to describe the essential dynamics. According to the timescale separation demonstrated here, we developed a two-phase model on the dynamics of DNA supercoiling, which can capture physiologically relevant events across timescales of several orders of magnitudes. In this model, we systematically characterized the slow dynamics between the two phases and compared the numerical results with those from the DNA polymer physics-based worm-like chain model. The supercoiling dynamics, including the nucleation, diffusion, and hopping of plectonemes, 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 multiscale physical mechanisms of the DNA supercoiling-dependent physiological processes.
DNA 超螺旋在转录和复制等基因组调控过程中产生，并为这些过程提供机械反馈。在张力作用下，DNA 超螺旋可以呈现出扭结和拉伸相的共存状态。实验揭示了扭结的动态行为，例如扩散、成核和跃迁。为了用构象变化来表示这些动力学，我们首先展示了 DNA 上的快速动力学，以在扭结和拉伸相中达到扭矩平衡，然后将双相边界确定为集体慢变量，以描述基本动力学。根据这里展示的时间尺度分离，我们在 DNA 超螺旋动力学上开发了一个双相模型，该模型可以在几个数量级的时间尺度上捕捉到与生理相关的事件。在该模型中，我们系统地描述了两相之间的慢动力学，并将数值结果与基于 DNA 聚合物物理的蠕虫链模型的结果进行了比较。扭结动力学，包括扭结的成核、扩散和跃迁，使用双相动力学模型以微不足道的计算成本得到了很好的表示和再现。因此，我们目前的发展可以用于探索 DNA 超螺旋依赖的生理过程的多尺度物理机制。
