Theoretical and computational validation of the Kuhn barrier friction mechanism in unfolded proteins
Theoretical and computational validation of the Kuhn barrier friction mechanism in unfolded proteins
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DOI：
10.1038/s41598-017-00287-5
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发表时间：
2017-03-21
影响因子：
4.6
通讯作者：
Makarov, Dmitrii E.
中科院分区：
文献类型：
--
作者：
Avdoshenko, Stanislav M.;Das, Atanu;Makarov, Dmitrii E.
很久以前，库恩预测，长聚合物应该接近一个极限，在这个极限中，它们的全球运动仅由溶剂摩擦控制，它们的能量景观的崎岖不会对它们的动力学产生影响。相反，对于中等长度的聚合物来说，内耗效应很重要。尤其是蛋白质中的内耗，会影响它们折叠或找到结合靶点的速度，因此最近引起了人们的极大关注。在这里，我们使用原子模拟、粗粒度模型和分析理论来探索未折叠蛋白质中内耗的分子起源。我们证明了特征内耗时间标度与多肽链内受阻二面体旋转的时间标度成正比，比例系数b与链长无关。B的这种链长无关性提供了可实验检验的证据，证明内耗是由协调的曲轴式二面体重排引起的。根据唯象内耗模型，我们发现多肽的全局重构时间是溶剂摩擦和内耗时间之和。同时，多肽中单体间距离的时间演化偏离了这些模型的预测，也偏离了简单的一维扩散模型。
long time ago, Kuhn predicted that long polymers should approach a limit where their global motion is controlled by solvent friction alone, with ruggedness of their energy landscapes having no consequences for their dynamics. In contrast, internal friction effects are important for polymers of modest length. Internal friction in proteins, in particular, affects how fast they fold or find their binding targets and, as such, has attracted much recent attention. Here we explore the molecular origins of internal friction in unfolded proteins using atomistic simulations, coarse-grained models and analytic theory. We show that the characteristic internal friction timescale is directly proportional to the timescale of hindered dihedral rotations within the polypeptide chain, with a proportionality coefficient b that is independent of the chain length. Such chain length independence of b provides experimentally testable evidence that internal friction arises from concerted, crankshaft-like dihedral rearrangements. In accord with phenomenological models of internal friction, we find the global reconfiguration timescale of a polypeptide to be the sum of solvent friction and internal friction timescales. At the same time, the time evolution of inter-monomer distances within polypeptides deviates both from the predictions of those models and from a simple, one-dimensional diffusion model.