2D IR OF UNUSUAL ISOTOPOMERS AND FOLDING

异常同位素异构体和折叠的二维红外图

• 批准号: 7598434
• 负责人: Amos B Smith
• 金额: $ 2.78万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7598434
• 关键词: Amides; Complex; Computer Retrieval of Information on Scientific Projects Database; Coupled; Coupling; Dependence; Development; Evolution; Frequencies; Funding; Grant; Institution; Isotopes; Label; Length; Measures; Methods; Molecular; Peptides; Process; Proteins; Range; Research; Research Personnel; Resolution; Resources; Source; Structure; System; Time; United States National Institutes of Health; chemical bond; infrared spectroscopy; isotope incorporation; protein folding; three dimensional structure; villin

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. To obtain a better understanding of the process of protein folding, development of physical methods that measure the time dependences of structural changes in complex systems is essential. Because of the intrinsically high time resolution, multidimensional infrared spectroscopy (2D IR and 3D IR) can contribute significantly to this challenge. IR spectra of proteins and peptides are intimately connected with their complete three-dimensional structures on the length scale of chemical bonds. However, the vibrational transitions of proteins are not always spectrally resolved. In this respect, multidimensional nonlinear infrared methods can provide additional information on how the various modes are coupled. Isotopic replacements have been essential in the interpretation of vibrational spectra and their relationship to structure. Isotopomers have frequencies, force fields, and anharmonicities that are different from one another. Incorporation of isotopes in 2D IR leads to shift in frequencies into regions where their couplings can be measured, free from interference by other modes of the system. For the amide I mode, the shifts by 13C=18O and 13C=16O substitution are sufficiently large to displace the substituted amide group frequencies beyond the range of the natural distribution of frequencies found in most secondary structures. The strategy of the Resource is to insert both 13C=18O and 13C=16O labels into secondary structures at known residues. Since their isotope shifts are different, a pair of isotopic peaks is created and 2D IR spectroscopic methods can then be used to analyze the coupling between those specific pairs of molecular transitions. Applying this approach, the real time evolution of folding of the secondary structure of the Villin headpiece can be examined using 2D IR.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 为了更好地理解蛋白质折叠的过程，发展物理方法来测量复杂系统中结构变化的时间依赖性是必不可少的。 由于固有的高时间分辨率，多维红外光谱（2D IR和3D IR）可以显着有助于这一挑战。 蛋白质和多肽的红外光谱与它们在化学键长度尺度上的完整三维结构密切相关。 然而，蛋白质的振动跃迁并不总是光谱解析的。 在这方面，多维非线性红外方法可以提供关于各种模式如何耦合的附加信息。 同位素置换在解释振动光谱及其与结构的关系中是必不可少的。 同位素异构体具有彼此不同的频率、力场和非谐性。 在二维IR中加入同位素导致频率转移到可以测量其耦合的区域，而不受系统其他模式的干扰。 对于酰胺I 模式，13 C = 18 O和13 C = 16 O取代的位移足够大，取代酰胺基团的频率超出了大多数二级结构中发现的频率的自然分布范围。 资源的策略是将13 C = 18 O和13 C = 16 O标记插入二级结构中的已知残基。 由于它们的同位素位移不同，因此产生了一对同位素峰，然后可以使用2D IR光谱方法来分析这些特定分子跃迁对之间的耦合。 应用这种方法，可以使用2D IR检查Villin头部的二级结构的折叠的真实的时间演化。