Watching water migration around a peptide bond.
Watching water migration around a peptide bond.
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DOI：
10.1002/anie.201203296
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发表时间：
2012-07
影响因子：
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通讯作者：
Kohei Tanabe;M. Miyazaki;M. Schmies;A. Patzer;Markus Schütz;H. Sekiya;M. Sakai;O. Dopfer;M. Fujii
中科院分区：
文献类型：
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作者：
Kohei Tanabe;M. Miyazaki;M. Schmies;A. Patzer;Markus Schütz;H. Sekiya;M. Sakai;O. Dopfer;M. Fujii
生命被认为起源于水环境，我们身体的70%是由水组成的。生物系统的基本组分必须在水溶液中通过分子间作用力与水分子相互作用，如氢键、分散力和亲疏水相互作用蛋白质是最重要的生物超分子之一，在肽链conh键的CO和NH位点上提供有吸引力的氢键位点，其中H2O可以分别作为质子供体或质子受体。蛋白质的溶剂化对其分子形状有强烈的影响，因此表面水网络的波动对其折叠性能和催化功能有重要影响最根本的是，当蛋白质开始折叠运动时，与蛋白质结合的水网络氢必须重新排列，从而影响动力学。因此，最新的蛋白质折叠及其功能的量子化学模拟明确地包括水分子。[2h, l， m]要在分子水平上对这些现象有更深入的了解，需要对单个水分子与蛋白质相互作用的动力学过程进行表征。然而，大多数实验只得到间接的动力学信息，平均在第一水合层的水分子，因此只是一个试探性的和经常有争议的潜在机制的解释。[2a, e, g, i, k， n]在真实的生物环境中对特定水分子的运动进行可视化测量是具有挑战性的，到目前为止还没有实验数据的报道。这种动态实验需要区分每一个单独的水分子，它们可以结合到蛋白质的许多不同的结合位点，并且很容易在相同或更高的水化溶剂化层中与其他水分子交换它们的作用。迄今为止，水合蛋白固有的复杂性阻碍了对溶液中单个水分子迁移的测量，因此，关于这一过程的几乎所有信息都依赖于理论方法。[2a, f-h， lo]尽管近年来由于计算机的快速发展，对此类复杂系统的量子化学模拟取得了实质性进展，但其准确性仍然相当有限，并且高度要求模型系统的实验基准数据用于校准目的。为此，我们在过去十年中开发了一种实验策略来研究动态分子间过程，[3]通常发生在皮秒（ps）时间尺度上。这种方法包括在超音速光束中分离分子团簇的产生，并使用ps时间分辨红外光谱表征其动力学。光谱学和量子化学卓有成效的结合目前为分子间相互作用提供了最直接和最详细的途径红外光谱对结构基序特别敏感在初步的基准实验中，我们开发了一种三色紫外-紫外-红外可调皮秒泵浦探测激光光谱仪[3a， b, e, g]，并测量了电离诱导的π！苯酚上稀有气体配体的H位转换动力学。[3a-d， 5]在这种情况下，通过酚羟基拉伸振动的结构敏感频率来监测配体的位置。虽然对于非常有限数量的芳香族分子的水配合物，激光诱导的水配体迁移最近已经用纳秒激光从“静态”光谱中推断出来，[4b, d， 6]没有关于动力学的时间分辨研究。
Life is believed to have its origin in aqueous environments, and 70% of our body consists of water. The essential components of biological systems have to interact in aqueous solutions with water molecules by intermolecular forces, such as hydrogen bonds, dispersion forces, and hydrophilic/hydrophobic interactions.[1] Proteins are one of the most important biological supramolecules and offer at the CO and NH sites of the-CONH-linkages of the peptide chain attractive hydrogen-bonding sites, in which H2O can act either as a proton donor or a proton acceptor, respectively. The solvation of a protein has a strong effect on its molecular shape, and as a consequence the fluctuations of the water network on the surface have important influence on its folding properties and catalytic function.[2] Most fundamentally, when a protein starts its folding motion, the water network hydrogen-bonded to the protein has to rearrange and thus affects the dynamics. Therefore, up-to-date quantum chemical simulations on protein folding and its functions include water molecules explicitly.[2h, l, m] A deeper understanding of these phenomena at the molecular level requires the characterization of the dynamical processes of individual water molecules interacting with the protein. However, most experiments yield only indirect dynamical information averaged over water molecules in the first hydration layer and thus only a tentative and often controversial interpretation of the underlying mechanisms.[2a, e–g, i, k, n] Measurements visualizing the motion of a specific water molecule in a real biological environment are challenging, and so far no experimental data have been reported yet. Such dynamical experiments need to distinguish between each single water molecule, which can bind to numerous different binding sites of the protein and readily exchange their role with other H2O molecules in the same or higher hydration solvation layers. This inherent complexity of the hydrated protein has so far prevented measurements of the migration of individual water molecules in solution, and therefore nearly all information about such processes relies on theoretical approaches.[2a, f–h, lo]Although quantum chemical simulations for such complex systems have substantially progressed in recent years because of rapid computer developments, their accuracy is still rather limited and experimental benchmark data for model systems are highly requested for calibration purposes. To this end, we have developed in the past decade an experimental strategy for the investigation of dynamical intermolecular processes,[3] which typically occur on the picosecond (ps) time scale. This approach involves the generation of molecular clusters isolated in supersonic beams and the characterization of their dynamics using ps time-resolved IR spectroscopy. The fruitful combination of spectroscopy and quantum chemistry currently provides the most direct and most detailed access to intermolecular interactions.[1] IR spectroscopy is particularly sensitive to structural motifs.[4] In initial benchmark experiments, we developed a three-color UV-UV-IR tunable picosecond pump–probe laser spectrometer [3a, b, e, g] and measured the ionization-induced π! H site switching dynamics of rare gas ligands attached to phenol.[3a–d, 5] In this case, the position of the ligand was monitored by the structure-sensitive frequency of the phenolic OH stretching vibration. Although for a very limited number of water complexes with aromatic molecules the laser-induced migration of the water ligand has recently been inferred from “static” spectroscopy using nanosecond lasers,[4b, d, 6] no time-resolved studies about the dynamics of …