How proteins modify water dynamics
How proteins modify water dynamics
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DOI：
10.1063/1.5026861
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发表时间：
2018-06-07
影响因子：
4.4
通讯作者：
Halle, Bertil
中科院分区：
文献类型：
--
作者：
Persson, Filip;Soderhjelm, Par;Halle, Bertil
生物学的大部分发生在蛋白质-水界面，因此这一区域的所有动力学过程都至关重要。水化层中的局部结构波动可以通过O-17磁弛豫色散（MRD）来探测，该磁弛豫色散在高频下测量双轴旋转时间相关函数（TCF）的积分-积分旋转相关时间。许多O-17 MRD研究表明，当在第一水化壳层上平均时，这种相关时间比在本体水中长3-5倍。分子动力学模拟证实了这种转动扰动因子（RPF）的存在，并揭示了其分子机制。在这里，我们通过分析一组广泛的分子动力学数据，包括四个球状蛋白质和三个水模型，解决了这一领域的几个突出问题。解决了棘手的问题的极性与地形作为主要的决定因素的水化水动力学的RPF上的一个简单的限制指数建立一个蛋白质不变的指数依赖。我们的结论是，先前观察到的RPF与表面极性的相关性是极性和限制之间的相关性的二次效应。水的旋转插入之间的扰动，但批量样的集体机制在低限制和交换介导的取向随机化（EMOR）机制在高限制。EMOR过程，约占一半的RPF，没有认识到在以前的模拟研究，其中只有早期的TCF部分进行了检查。基于实验相关的TCF在其整个时间过程中的分析，我们比较模拟和测量的RPF，发现30%的差异归因于力场的缺陷。我们还计算了完整的O-17 MRD配置文件，包括埋水分子产生的低频色散。计算每个水化壳的局部RPF，我们发现，扰动指数衰减的衰减“长度”为0.3壳，第二和更高的壳仅占3%的O-17 MRD测量的总扰动。唯一的长程效应是在电中性蛋白质（未被反离子屏蔽）产生的电场中的弱水排列，但这种效应对于O-17 MRD来说小得可以忽略。相比之下，我们发现，O-17 TCF是显着更敏感的重要的短程扰动比其他两个TCF在这里检查。(C)2018年作者。
Much of biology happens at the protein-water interface, so all dynamical processes in this region are of fundamental importance. Local structural fluctuations in the hydration layer can be probed by O-17 magnetic relaxation dispersion (MRD), which, at high frequencies, measures the integral of a biaxial rotational time correlation function (TCF)-the integral rotational correlation time. Numerous O-17 MRD studies have demonstrated that this correlation time, when averaged over the first hydration shell, is longer than in bulk water by a factor 3-5. This rotational perturbation factor (RPF) has been corroborated by molecular dynamics simulations, which can also reveal the underlying molecular mechanisms. Here, we address several outstanding problems in this area by analyzing an extensive set of molecular dynamics data, including four globular proteins and three water models. The vexed issue of polarity versus topography as the primary determinant of hydration water dynamics is resolved by establishing a protein-invariant exponential dependence of the RPF on a simple confinement index. We conclude that the previously observed correlation of the RPF with surface polarity is a secondary effect of the correlation between polarity and confinement. Water rotation interpolates between a perturbed but bulk-like collective mechanism at low confinement and an exchange-mediated orientational randomization (EMOR) mechanism at high confinement. The EMOR process, which accounts for about half of the RPF, was not recognized in previous simulation studies, where only the early part of the TCF was examined. Based on the analysis of the experimentally relevant TCF over its full time course, we compare simulated and measured RPFs, finding a 30% discrepancy attributable to force field imperfections. We also compute the full O-17 MRD profile, including the low-frequency dispersion produced by buried water molecules. Computing a local RPF for each hydration shell, we find that the perturbation decays exponentially with a decay "length" of 0.3 shells and that the second and higher shells account for a mere 3% of the total perturbation measured by O-17 MRD. The only long-range effect is a weak water alignment in the electric field produced by an electroneutral protein (not screened by counterions), but this effect is negligibly small for O-17 MRD. By contrast, we find that the O-17 TCF is significantly more sensitive to the important short-range perturbations than the other two TCFs examined here. (C) 2018 Author(s).