Changing the Mechanical Unfolding Pathway of FnIII10 by Tuning the Pulling Strength
Changing the Mechanical Unfolding Pathway of FnIII10 by Tuning the Pulling Strength
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DOI：
10.1016/j.bpj.2008.09.043
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发表时间：
2009-01-21
影响因子：
3.4
通讯作者：
Irbaeck, Anders
中科院分区：
文献类型：
--
作者：
Mitternacht, Simon;Luccioli, Stefano;Irbaeck, Anders
我们通过全原子蒙特卡罗模拟研究了纤连蛋白第十个 III 型结构域 (FnIII(10)) 在恒定力和恒定拉速下的机械展开。我们观察到明显的两种状态展开和涉及三个主要的、相互排斥的中间状态之一的几种展开路径。所有三种主要中间体都缺乏七个天然β链中的两个，并且具有非常相似的延伸。发现展开行为很大程度上取决于拉力条件。特别是，我们观察到中间体出现的相对频率存在很大变化。在低恒力或低恒速度下，所有三种主要中间体都会以显着的频率出现。在高恒定力或高恒定速度下，其中一个 N 端和 C 端 β 链分离，优于其他两个。使用扩展的 Jarzynski 等式，我们还估计了平衡自由能景观，计算为链延伸的函数。施加恒定拉力会产生具有三个主要局部最小值的自由能分布。其中两个分别对应于天然和完全展开状态，而第三个可以与主要展开中间体相关。
We investigate the mechanical unfolding of the tenth type III domain from fibronectin (FnIII(10)) both at constant force and at constant pulling velocity, by all-atom Monte Carlo simulations. We observe both apparent two-state unfolding and several unfolding pathways involving one of three major, mutually exclusive intermediate states. All three major intermediates lack two of seven native beta-strands, and share a quite similar extension. The unfolding behavior is found to depend strongly on the pulling conditions. In particular, we observe large variations in the relative frequencies of occurrence for the intermediates. At low constant force or low constant velocity, all three major intermediates occur with a significant frequency. At high constant force or high constant velocity, one of them, with the N- and C-terminal beta-strands detached, dominates over the other two. Using the extended Jarzynski equality, we also estimate the equilibrium free-energy landscape, calculated as a function of chain extension. The application of a constant pulling force leads to a free-energy profile with three major local minima. Two of these correspond to the native and fully unfolded states, respectively, whereas the third one can be associated with the major unfolding intermediates.