ETH Zurich, Laboratorium für Physikalische Chemie, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland.
Chemistry. 2009 Dec 14;15(48):13491-508. doi: 10.1002/chem.200901840.
A prerequisite for the understanding of functional molecules like proteins is the elucidation of their structure under reaction conditions. Chiral vibrational spectroscopy is one option for this purpose, but provides only indirect access to this structural information. By first-principles calculations, we investigate how Raman optical activity (ROA) signals in proteins are generated and how signatures of specific secondary-structure elements arise. As a first target we focus on helical motifs and consider polypeptides consisting of twenty alanine residues to represent alpha-helical and 3(10)-helical secondary-structure elements. Although ROA calculations on such large molecules have not been carried out before, our main goal is the stepwise reconstruction of the ROA signals. By analyzing the calculated ROA spectra in terms of rigorously defined localized vibrations, we investigate in detail how total band intensities and band shapes emerge. We find that the total band intensities can be understood in terms of the reconstructed localized vibrations on individual amino acid residues. Two different basic mechanisms determining the total band intensities can be established, and it is explained how structural changes affect the total band intensities. The band shapes can be rationalized in terms of the coupling between the localized vibrations on different residues, and we show how different band shapes arise as a consequence of different coupling patterns. As a result, it is demonstrated for the chiral variant of Raman spectroscopy how collective vibrations in proteins can be understood in terms of well-defined localized vibrations. Based on our calculations, we extract characteristic ROA signatures of alpha helices and of 3(10)-helices, which our analysis directly relates to differences in secondary structure.
理解蛋白质等功能分子的前提条件是阐明它们在反应条件下的结构。手性振动光谱是达到此目的的一种选择,但只能提供对此结构信息的间接访问。通过第一性原理计算,我们研究了蛋白质中的拉曼光学活性(ROA)信号是如何产生的,以及特定二级结构元素的特征是如何出现的。作为第一个目标,我们专注于螺旋结构,并考虑由二十个丙氨酸残基组成的多肽来代表α-螺旋和 3(10)-螺旋二级结构元件。尽管以前没有对如此大的分子进行 ROA 计算,但我们的主要目标是逐步重建 ROA 信号。通过根据严格定义的局部振动来分析计算的 ROA 光谱,我们详细研究了总带强度和带形状是如何出现的。我们发现,总带强度可以用单个氨基酸残基上重建的局部振动来理解。可以确定两种不同的基本机制来决定总带强度,并且解释了结构变化如何影响总带强度。可以根据不同残基上的局部振动之间的耦合来合理化带形状,并且我们展示了不同的带形状如何由于不同的耦合模式而出现。因此,在手性拉曼光谱学的情况下,证明了如何根据明确的局部振动来理解蛋白质中的集体振动。基于我们的计算,我们提取了α螺旋和 3(10)螺旋的特征 ROA 特征,我们的分析直接将其与二级结构的差异联系起来。