分子溜溜球方法：实时跳跃检测提高了单分子力谱法对非平衡跃迁的通量
The molecular yo-yo method: Live jump detection improves throughput of single-molecule force spectroscopy for out-of-equilibrium transitions
摘要：
通过监测多个分子跃迁，力钳和陷阱-位置-钳方法已经导致在相同或相似的力下处于平衡状态的分子的自由能和自由能景观的精确测定。在这里，我们提出了一个强大的新的阐述力钳和力跳的方法，适用于过渡远离平衡。具体来说，我们已经实现了一种实时跳跃检测和力钳算法，该算法可以智能地调整和保持单个分子上的力，以响应该分子的测量状态。我们能够收集数百个不同力下的单个分子跃迁，比以前快很多倍，使我们能够准确地确定力依赖的寿命分布和反应速率。应用我们的方法解开和倒带的核小体内转，使用光镊揭示了实验寿命分布，包括一个有意义的数量的过渡，并准确地单指数。这些测量显着减少了以前测量的速率的误差，并证明了存在一个单一的，占主导地位的自由能障碍在每个研究的力量。核小体的分子yoyo方法的一个关键好处是，它尽可能减少了在切向结合状态下花费的时间，从而最大限度地减少了核小体的解离损失。
英文摘要：
By monitoring multiple molecular transitions, force-clamp and trap-position-clamp methods have led to precise determinations of the free energies and free energy landscapes for molecular states populated in equilibrium at the same or similar forces. Here, we present a powerful new elaboration of the force-clamp and force-jump methods, applicable to transitions far from equilibrium. Specifically, we have implemented a live jump detection and force-clamp algorithm that intelligently adjusts and maintains the force on a single molecule in response to the measured state of that molecule. We are able to collect hundreds of individual molecular transitions at different forces, many times faster than previously, permitting us to accurately determine force-dependent lifetime distributions and reaction rates. Application of our method to unwinding and rewinding the nucleosome inner turn, using optical tweezers reveals experimental lifetime distributions that comprise a statistically-meaningful number of transitions, and that are accurately single exponential. These measurements significantly reduce the error in the previously measured rates, and demonstrate the existence of a single, dominant free energy barrier at each force studied. A key benefit of the molecular yoyo method for nucleosomes is that it reduces as far as possible the time spent in the tangentially-bound state, which minimizes the loss of nucleosomes by dissociation.
机构、总结、中文摘要均由AI分析而来，可能存在错误，请以论文正文为准。
