Unfolding single RNA molecules: bridging the gap between equilibrium and non-equilibrium statistical thermodynamics
Unfolding single RNA molecules: bridging the gap between equilibrium and non-equilibrium statistical thermodynamics
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DOI：
10.1017/s0033583506004239
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发表时间：
2005-11-01
影响因子：
6.1
通讯作者：
Bustamante, Carlos
中科院分区：
文献类型：
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作者：
Bustamante, Carlos
在过去的15年里，科学家们已经开发出了允许对单个分子进行直接机械操作的方法。使用这种方法，他们已经开始研究力和扭矩在化学反应和生化反应中的影响。这些研究的范围从大分子的机械性质的研究，到分子马达的表征，再到单个蛋白质和RNA的机械展开。在这里，我将回顾我们使用机械力来展开单个RNA分子的一些最新结果。这些研究使人们有可能实时跟踪每个分子展开时的轨迹，并表征反应的各种中间产物。此外，如果这个过程可逆地发生，就有可能从这些实验中同时提取动力学和热力学信息，同时我们可以表征维持溶液中分子三维结构的力。这些研究使我们更接近细胞中的生物去折叠过程，因为他们在体外模拟了由解旋酶在细胞中进行的RNA的机械去折叠。如果展开过程不可逆地发生，我在这里表明，单分子实验仍然可以通过使用最近发现的涨落定理，从非平衡数据中提供平衡热力学信息。这些定理代表了平衡和非平衡统计力学之间的桥梁。事实上，涨落定理有效性的第一个实验证明是在1997年首次推导出来的，它是通过机械地展开单个RNA分子而获得的。这也许是一个时代的标志，如今重要的物理结果被用来提取关于生物系统的信息，生物系统正被用来测试和确认物理学中的基本新定律。
During the last 15 years, scientists have developed methods that permit the direct mechanical manipulation of individual molecules. Using this approach, they have begun to investigate the effect of force and torque in chemical and biochemical reactions. These studies span from the study of the mechanical properties of macromolecules, to the characterization of molecular motors, to the mechanical unfolding of individual proteins and RNA. Here I present a review of some of our most recent results using mechanical force to unfold individual molecules of RNA. These studies make it possible to follow in real time the trajectory of each molecule as it unfolds and characterize the various intermediates of the reaction. Moreover, if the process takes place reversibly it is possible to extract both kinetic and thermodynamic information from these experiments at the same time that we characterize the forces that maintain the three-dimensional structure of the molecule in solution. These studies bring us closer to the biological unfolding processes in the cell as they simulate in vitro, the mechanical unfolding of RNAs carried out in the cell by helicases. If the unfolding process occurs irreversibly, I show here that single-molecule experiments can still provide equilibrium, thermodynamic information from non-equilibrium data by using recently discovered fluctuation theorems. Such theorems represent a bridge between equilibrium and non-equilibrium statistical mechanics. In fact, first derived in 1997, the first experimental demonstration of the validity of fluctuation theorems was obtained by unfolding mechanically a single molecule of RNA. It is perhaps a sign of the times that important physical results are these days used to extract information about biological systems and that biological systems are being used to test and confirm fundamental new laws in physics.