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

化学系的实验物理化学项目支持伊利诺伊大学芝加哥分校化学系教授Timothy Keiderling的研究。Keiderling和他的学生将利用红外、拉曼、振动圆二色谱(VCD)和荧光技术，研究不同长度和不同氨基酸残基序列的柔性多肽分子，这些分子旨在折叠成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。该项目将强调使用选择性地用碳-13标记的多肽，这些多肽可以用IR、拉曼或VCD光谱来研究，以确定特定部位的局部多肽结构。在平衡条件下，通过改变温度、溶剂和pH可以引起构象变化。与时间相关的温度跳跃光谱将被用来研究解开多肽结构的动力学。这些实验将与从头算量子力学计算相结合，以模拟各种构象分子中多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多肽和蛋白质状态的关键成分。从这些研究中获得的信息将提高我们对蛋白质折叠以及生物化学和结构生物学影响领域的理解。

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.