Site-Selective Peptide Conformations and Dynamics with Isotopic Labeling and Vibrational Spectroscopy

化学部的实验物理化学计划支持芝加哥伊利诺伊大学化学系的Timothy Keiderling教授的研究。利用红外、拉曼、振动圆二色性（VCD）和荧光技术，Keiderling和他的学生将研究不同长度的柔性肽分子和不同序列的氨基酸残基，这些氨基酸残基被设计成折叠成β-发夹结构。这些分子将为研究β折叠的基本步骤提供模型。该项目将强调使用多肽，选择性地用碳-13标记，可以用IR，拉曼或VCD光谱学进行研究，以确定位点特异性，局部肽结构。在平衡条件下，通过改变温度、溶剂和pH值将诱导构象变化。时间依赖性，温度跳跃光谱将用于研究展开的肽结构的动力学。这些实验将结合从头算量子力学计算，以模拟具有各种构象的分子中肽键之间的短程和长程相互作用。分子动力学方法将被用来模拟多肽折叠的机制。β折叠是几种有毒的错误折叠的肽和蛋白质状态的关键组分。从这些研究中获得的信息将提高我们对蛋白质折叠的理解，并影响生物化学和结构生物学领域。

The Experimental Physical Chemistry program of the Division of Chemistry supports the research of Professor Timothy Keiderling of the Department of Chemistry, University of Illinois at Chicago. Using infrared, Raman, vibrational circular dichroism (VCD), and fluorescence techniques, Keiderling and his students will study flexible peptide molecules of different lengths and varying sequences of amino acid residues that are designed to fold into beta-hairpin structures. These molecules will provide models for the study of the elementary steps in beta-sheet folding. The project will emphasize the use of polypeptides, selectively labeled with carbon-13, which can be studied with IR, Raman, or VCD spectroscopy to determine site-specific, local peptide structures. Conformational changes will be induced by varying the temperature, solvent, and pH under equilibrium conditions. Time-dependent, temperature jump spectroscopy will be used to investigate the dynamics of unfolding the peptide structure. These experiments will be combined with ab-initio quantum mechanical calculations to model short- and long-range interactions between peptide bonds in molecules with a variety of conformations. Molecular dynamics methods will be employed to simulate the mechanisms for polypeptide folding. Beta-sheets are critical components for several toxic mis-folded peptide and protein states. The information gained from these studies will improve our understanding of protein folding and impact areas of biochemistry and structural biology.