Explicit Characterization of the Free-Energy Landscape of a Protein in the Space of All Its Cα Carbons.,Journal of Chemical Theory and Computation

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Explicit Characterization of the Free-Energy Landscape of a Protein in the Space of All Its Cα Carbons.
Journal of Chemical Theory and Computation ( IF 5.7 ) Pub Date : 2019-12-20 , DOI: 10.1021/acs.jctc.9b00800
Giulia Sormani ₁ , Alex Rodriguez ₂ , Alessandro Laio ₁

Affiliation

By using an approach that allows computing the free energy in high-dimensional spaces together with a clustering technique capable of identifying kinetic attractors stabilized by conformational disorder, we analyze a molecular dynamics trajectory of the Villin headpiece from Lindorff-Larsen, K.; et al. How fast-folding proteins fold. Science 2011, 334, 517-520. We compute its free-energy landscape in the space of all its Cα carbons. This landscape has the shape of a 12-dimensional funnel with the free energy decreasing monotonically as a function of the native contacts. There are no significant folding barriers. The funnel can be partitioned in five regions, three mainly folded and two unfolded, which behave as Markov states. The slowest relaxation time among these states corresponds to the folding transition. The second slowest time is only twice smaller and corresponds to a transition within the unfolded state. This indicates that the unfolded part of the funnel has a nontrivial shape, which induces a sizable kinetic barrier between disordered states.

中文翻译：

蛋白质在其所有Cα碳空间中的自由能态的显式表征。

通过使用一种允许在高维空间中计算自由能的方法以及一种能够识别由构象障碍稳定的动力学吸引子的聚类技术，我们分析了来自Lindorff-Larsen，K.的Villin头盔的分子动力学轨迹。等。快速折叠的蛋白质如何折叠。科学，2011，334，517-520。我们在其所有Cα碳的空间中计算其自由能态势。该景观具有12维漏斗的形状，其自由能根据本机接触而单调减少。没有明显的折叠障碍。漏斗可以划分为五个区域，三个区域主要是折叠的，两个处于展开状态，表现为马尔可夫状态。这些状态中最慢的松弛时间对应于折叠转变。第二最慢的时间仅短两倍，并且对应于展开状态内的过渡。这表明漏斗的展开部分具有非平凡的形状，从而在无序状态之间引发了相当大的动力学屏障。

更新日期：2019-12-20

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