Ultrafast Processing in Proteins and Other Assemblies

跨膜（TM）螺旋的蛋白质结构如何随时间变化的残基水平可视化，快速 折叠蛋白质和二级结构的元素将通过二维红外光谱被发现 (2D IR）一种新的，强大的结构生物学方法。肽和蛋白质的同位素标记增强了 2D IR的空间分辨率，并将其扩展到更大的肽。螺旋-螺旋界面的弱键 将访问血型糖蛋白A的TM部分以获得界面区域中基团的运动， 发现它们如何稳定TM蛋白中的螺旋-螺旋相互作用。2D IR暴露了脂质波动， 膜上的空间排列。疏水效应、极性、氢键和 埋藏残基之间的其他弱相互作用揭示了螺旋的机制和结构基础 协会具有多个IR频率的2D IR，访问疏水界面，相关性 在不同的空间位置的波动和跨膜螺旋中的N-H/N-D交换之间。 独立折叠的蛋白质亚结构域是解决折叠问题的重要工具。2D IR快速开启 非指数文件夹将允许访问二级结构的真实的时间演化， 原子分子动力学的绒毛头部从肌动蛋白捆绑蛋白绒毛，这是牵连 肠道和肾脏的上皮细胞折叠途径将通过同位素标记的2D IR来访问 螺旋和疏水核。在氧化还原蛋白，细胞色素c，途径中间体，将 用新的温度诱导的pH跳跃进行检查。将描述设计的肽的折叠。 通过二维红外寻求可视化他们如何组装和加强与理论的关系。研究涉及 膜蛋白是细胞生理学的重要组成部分：它们包括细胞表面受体，离子 通道、转运蛋白和氧化还原蛋白。整合膜蛋白占所有蛋白质的近四分之一 在高等生物中，超过一半的商业药物都是针对这类生物的。 proteins.尽管如此，对它们的3D结构和动力学的研究仍然有限。蛋白质折叠是 这是将遗传信息转化为所有人的生物功能的关键一步， 类型，因此其控制是了解人类健康的重要组成部分。*

A residue level visualization of how protein structures change with time for transmembrane (TM) helices, fast folding proteins and elements of secondary structure will be found by two dimensional infrared spectroscopy (2D IR) a new, powerful method of structural biology. Isotopic labeling of peptides and proteins enhances the spatial resolution of 2D IR and extends it to larger peptides. Weak bonds involved at the helix-helix interfaces of TM sections of Glycophorin A will be accessed to obtain the motions of groups in the interface regions and discover how they stabilize helix-helix interactions in TM proteins. 2D IR exposes lipid fluctuations in terms of spatial arrangements across the membrane. 2D IR of hydrophobic effects, polarity, hydrogen bonding and other weak interactions between buried residues enlighten the mechanisms and structural basis of helix association. The 2D IR with multiple IR frequencies, accesses the hydrophobic interface, correlations between fluctuations at different spatial locations and the N-H/N-D exchange in transmembrane helices. Protein subdomains that fold independently are important tools for solving the folding problem. 2D IR on fast non-exponential folders will permit access to the real time evolution of secondary structure and challenge all atom molecular dynamics of the villin headpiece from the actin-bundling protein villin, which is implicated in the epithelium of the gut and kidney. The folding pathway will be accessed by 2D IR of isotope labeled helices and hydrophobic core. On-pathway intermediates in the redox protein, cytochrome-c, will be examined with novel temperature induced pH jumps. A description of the folding of designed peptides will be sought by 2D IR to visualize how they assemble and strengthen relations to theory. The research involves membrane proteins which are vital components of the cell physiology: they include cell-surface receptors, ion channels, transporters and redox proteins. Integral membrane proteins account for nearly one-quarter of all coding sequences in higher organisms, and more than half of all commercial drugs target this class of proteins. Despite this, study of their 3D structures and their dynamics remains limited. Protein folding is highly relevant because it is a key step in the conversion of genetic information into biological function of all types and therefore its control is an essential part of understanding human health. *