Visualizing protein motion in Couette flow by all-atom molecular dynamics
Visualizing protein motion in Couette flow by all-atom molecular dynamics
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通过全原子分子动力学可视化库埃特流中的蛋白质运动
DOI：
10.1016/j.bbagen.2019.06.006
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Sugase Kenji
中科院分区：
文献类型：
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作者：
Walinda Erik;Morimoto Daichi;Shirakawa Masahiro;Scheler Ulrich;Sugase Kenji
在活细胞中，生物大分子暴露于高度拥挤的环境中。细胞质、细胞核和其他细胞器是高度粘稠的液体，不同于体外条件下的稀释液。粘度是衡量流体内部摩擦力的一个指标，它直接影响作用在浸没的大分子上的力。虽然这种粘性流体的主动运动-细胞质流动-发生在许多植物和动物细胞中，但流体运动（流动）对生物分子的影响很少讨论。近年来，应用剪切流动原位核磁共振实验已被用于蛋白质的研究。虽然这些NMR实验已经成功地在光谱上跟踪蛋白质聚集在真实的时间，他们不提供剪切下的蛋白质运动的视觉图片。为了填补这一空白，在这里，我们已经使用分子动力学模拟来研究三种不同大小和形状的蛋白质在简单剪切流中的运动。蛋白质表现出随机扩散和剪切流诱导的旋转运动的叠加。随机旋转扩散在较低的剪切应力占主导地位，而一个积极的“滚动运动”沿着所施加的流的轴发生在较高的剪切应力。甚至更大的剪切应力扰动蛋白质二级结构元件，导致局部和全局展开。除了剪切诱导的解折叠之外，我们的结果还意味着，在理想的库埃特流场中，生物分子会经历相关运动，这应该会增强分子间相互作用和聚集的可能性。将生物分子模拟与应用剪切流的实验相结合，似乎是研究剪切下蛋白质排列、变形和动力学的一种有前途的策略。
In living cells, biomacromolecules are exposed to a highly crowded environment. The cytoplasm, the nucleus, and other organelles are highly viscous fluids that differ from dilutein vitroconditions. Viscosity, a measure of fluid internal friction, directly affects the forces that act on immersed macromolecules. Although active motion of this viscous fluid – cytoplasmic streaming – occurs in many plant and animal cells, the effect of fluid motion (flow) on biomolecules is rarely discussed. Recently NMR experiments that apply a shearing flowin situhave been used for protein studies. While these NMR experiments have succeeded in spectroscopically tracking protein aggregation in real time, they do not provide a visual picture of protein motion under shear. To fill this gap, here we have used molecular dynamics simulations to study the motion of three proteins of different size and shape in a simple shearing flow. The proteins exhibit a superposition of random diffusion and shear-flow-induced rotational motion. Random rotational diffusion dominates at lower shear stresses, whereas an active “rolling motion” along the axis of the applied flow occurs at higher shear stress. Even larger shear stresses perturb protein secondary structure elements resulting in local and global unfolding. Apart from shear-induced unfolding, our results imply that, in an ideal Couette flow field biomolecules undergo correlated motion, which should enhance the probability of inter-molecular interaction and aggregation. Connecting biomolecular simulation with experiments applying shear flowin situappears to be a promising strategy to study protein alignment, deformation, and dynamics under shear.