Kinetics from nonequilibrium single-molecule pulling experiments
Kinetics from nonequilibrium single-molecule pulling experiments
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DOI：
10.1016/s0006-3495(03)74449-x
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发表时间：
2003-07-01
影响因子：
3.4
通讯作者：
Szabo, A
中科院分区：
文献类型：
--
作者：
Hummer, G;Szabo, A
激光镊子或原子力显微镜施加的机械力可以用来驱动单个分子中罕见的转变，如蛋白质的展开或配体的解离。基于贝尔的力诱导破裂率表达式的拉力实验的唯象描述，当与简单的动力学微观模型的计算机模拟相比较时，被发现是不充分的。我们介绍了一种新的方法，该方法具有相当的复杂性，可以从拉实验中提取更准确的分子事件动力学信息。我们的程序基于一个简单的随机模型的分析，并包含了唯象方法，在适当的限度内将其简化为简谐弹簧拉力。我们的方法被用计算机模拟带有非调和连接子的多模块Titin模型进行了测试，然后对127个蛋白质Titin亚基的强制展开进行了说明性的应用。我们从拉力实验中提取动力学信息的过程很容易实现，应该在各种系统上的实验分析中被证明是有用的。
Mechanical forces exerted by laser tweezers or atomic force microscopes can be used to drive rare transitions in single molecules, such as unfolding of a protein or dissociation of a ligand. The phenomenological description of pulling experiments based on Bell's expression for the force-induced rupture rate is found to be inadequate when tested against computer simulations of a simple microscopic model of the dynamics. We introduce a new approach of comparable complexity to extract more accurate kinetic information about the molecular events from pulling experiments. Our procedure is based on the analysis of a simple stochastic model of pulling with a harmonic spring and encompasses the phenomenological approach, reducing to it in the appropriate limit. Our approach is tested against computer simulations of a multimodule titin model with anharmonic linkers and then an illustrative application is made to the forced unfolding of 127 subunits of the protein titin. Our procedure to extract kinetic information from pulling experiments is simple to implement and should prove useful in the analysis of experiments on a variety of systems.