Protein Structure, Dynamics, and Folding via Ultrafast Multidimensional Infrared Spectroscopy

在该奖项中，生命过程化学项目支持加州大学欧文分校的葛念辉教授使用飞秒多维红外（MultiD IR）光谱研究肽的构象动力学、分布和折叠。目标是提供蛋白质结构和动力学的详细知识，这对理解生物过程至关重要。拟议的工作包括调查螺旋和扩展结构之间的相互作用，确定非折叠肽的构象分布，并阐明蛋白质-膜相互作用。MultiD IR实验可访问肽的主链和侧链振动模式，并提供揭示结构单元之间的角度、距离和相关性的数据。同位素编辑和在选定的位置掺入IR探针增强了空间分辨率，促进了共振的分配，并将该方法扩展到更大的肽和三级接触。研究了温度、pH、溶剂和链长的影响，以了解控制蛋白质稳定性的因素。蛋白质，长链的肽，迅速折叠成复杂的形状，影响他们的功能，以及如何与其他分子结合。肽和更大的蛋白质的详细知识-结构，动力学和折叠可以揭示蛋白质错误折叠的特点，许多疾病。了解蛋白质如何与膜相互作用也为新功能分子的设计提供了信息，这些分子可能对医学有用。多维红外光谱是一种激光技术，可以通过研究在使用激光脉冲以快于万亿分之一秒的“快门速度”“拍照”后发出的红外光来确定肽的形状和行为。参与研究的研究生和博士后研究人员获得了先进激光技术和核心物理科学的宝贵经验，可以加强他们未来的职业发展。该项目还与维护在线频谱数据库和为K-12学生提供讲座和实验室课程的外联工作相结合。

In this award the Chemistry of Life Processes Program supports Professor Nien-Hui Ge of the University of California at Irvine to use femtosecond multidimensional infrared (MultiD IR) spectroscopy to study the conformational dynamics, distributions, and folding of peptides. The goal is to provide detailed knowledge of protein structure and dynamics that is essential to the understanding of biological processes. The proposed work includes investigating the interplay between helical and extended structures, determining conformational distributions of nonfolding peptides, and elucidating protein-membrane interactions. MultiD IR experiments access the backbone and side chain vibrational modes of peptides, and provide data that reveal the angles, distances, and correlations between structural units. Isotope editing and incorporating IR probes at selected locations enhance the spatial resolution, facilitate the assignment of resonances, and extend the method to larger peptides and tertiary contacts. The effects of temperature, pH, solvent, and chain length are investigated to understand the factors that control protein stability. Proteins, long chains of peptides, fold rapidly into complex shapes that affect their function and how they bind with other molecules. Detailed knowledge of peptides and larger proteins - structure, dynamics, and folding can shed light on protein misfolding that characterizes many diseases. Understanding how proteins interact with membranes also informs the design of novel functional molecules, potentially useful for medicine. MultiD IR spectroscopy is a laser technique that can determine the shape and behavior of a peptide by studying the infrared light emitted after it was "photographed" using laser pulses at a "shutter speed" faster than one trillionth of a second. Graduate students and postdoctoral researchers participating in the research gain valuable experience with advanced laser techniques and core physical sciences that can strengthen their future career development. This project is also integrated with outreach efforts on maintaining an online spectrum database and contributing lectures and laboratory courses for K-12 students.