发表机构
Eindhoven University of Technology; UHasselt, Faculty of Sciences, Data Science Institute, Theory Lab（埃因霍温理工大学; 荷语布鲁塞尔自由大学理学院数据科学研究所理论实验室）
机构由 AI 辅助整理，请以论文原文为准。AI 中文总结
研究 DNA 环化时间受间接力传递的影响，通过分子动力学模拟和分析框架，揭示侧翼片段对环化时间力依赖性的作用，用粗粒化 DNA 模型获与实验相符的预测，表明力传递几何结构对环化动力学有显著影响。
AI 中文摘要
DNA 环化形成是基因调控中的关键机制，环化动力学对作用于 DNA 的机械张力敏感。在单分子实验和生物环境中，这种张力通常通过环化区域两侧的 DNA 片段传递，而非直接作用于环化位点。尚未系统研究这种间接力传递如何影响环化时间。通过对蠕虫状链的分子动力学模拟表明，侧翼片段显著加剧了环化时间的力依赖性，该效应在其长度超过持久长度后对长度不敏感，当与环化区域的连接变得灵活时消失。开发了一个分析框架，通过环化片段有效自由能景观中的力依赖位移来解释这种效应。在小力极限下，这种位移简化为零力平衡平均值，之后环化时间的整个力依赖性可解析得出。使用将单个碱基视为刚体的粗粒化 DNA 模型应用此框架，得到与实验环化数据定量一致的预测。结果表明力传递的几何结构对环化动力学有显著且可预测的影响，对单分子实验和基因调控背景下依赖张力的环化解释有直接意义。
英文摘要
DNA loop formation is central to gene regulation, and its kinetics depend sensitively on mechanical tension. In both single-molecule experiments and biological settings, this tension is typically transmitted through flanking DNA segments rather than acting directly at the looping sites. Using molecular dynamics simulations of the wormlike chain model, we show that such flanking segments substantially enhance the force dependence of looping, with the effect saturating once their length reaches approximately one DNA persistence length and disappearing when the connection is made flexible. We develop an analytic theory in which the handles extend the effective looping coordinate. This extension is set by two quantities: an equilibrium property of the construct that can be measured without force, and the force-dependent length over which a handle remembers the orientation of its binding site. The resulting theory quantitatively reproduces published optical-tweezer measurements, without adjustable parameters. Furthermore, we demonstrate that the longstanding discrepancy between theory and experiment does not originate from neglected DNA-specific elastic effects, but is explained by the indirect transmission of force through the handles, establishing it as the dominant missing ingredient in the theory of DNA looping under force.
Comments12 pages, 4 figures
