Mitternacht Simon, Luccioli Stefano, Torcini Alessandro, Imparato Alberto, Irbäck Anders
Computational Biology and Biological Physics, Department of Theoretical Physics, Lund University, Lund, Sweden.
Biophys J. 2009 Jan;96(2):429-41. doi: 10.1016/j.bpj.2008.09.043.
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.
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)）在恒力和恒速拉伸条件下的机械展开过程。我们观察到了明显的两态展开以及几种涉及三种主要的、相互排斥的中间态之一的展开途径。所有这三种主要中间体都缺少七条天然β链中的两条，并且具有相当相似的伸展程度。发现展开行为强烈依赖于拉伸条件。特别是，我们观察到中间体出现的相对频率有很大变化。在低恒力或低恒速下，所有三种主要中间体都有相当高的出现频率。在高恒力或高恒速下，其中一种N端和C端β链分离的中间体比另外两种占主导地位。使用扩展的雅津斯基等式，我们还估计了作为链伸展函数计算的平衡自由能景观。施加恒定拉力会导致具有三个主要局部最小值的自由能分布。其中两个分别对应天然态和完全展开态，而第三个可以与主要展开中间体相关联。
