Two-Dimensional Infrared Spectroscopy of the Conformational Dynamics of Biomolecules

生物分子构象动力学的二维红外光谱

• 批准号: 1561888
• 负责人: Andrei Tokmakoff
• 金额: $ 62.06万
• 依托单位: University of Chicago
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-15 至 2019-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1561888&HistoricalAwards=false
• 关键词: Two; Dimensional; Infrared; Spectroscopy; Conformational

This award supports the research effort of Professor Andrei Tokmakoff aimed at developing the experimental method of two-dimensional infrared spectroscopy (2D IR) for the purposes of visualizing how DNA and proteins change their structure in real time. As important as these processes are in materials chemistry, biomedical research, and nanotechnology, few experiments are currently capable of studying how macromolecules change their structure during the course of chemical reactions and physical processes, since they occur on nanosecond to microsecond time-scales in solution. This work supports two graduate students as they learn about solution-phase chemical dynamics, macromolecular structure, and protein and DNA conformational changes. Additionally, this grant plays a role in supporting two continually expanding online textbooks, "Time-Dependent Quantum Mechanics and Spectroscopy" and "Concepts in Biophysical Chemistry".The specific scientific objective of this grant is to continue the ongoing development of transient 2D IR spectroscopy. The current method uses a temperature-jump (T-jump) to initiate conformational changes of proteins and DNA, and tracks the resulting changes in molecular structure with 2D IR. First, T-jump transient 2D IR experiments are used to study the conformational dynamics of DNA oligonucleotides, including hybridization, bubbling, fraying, and base flipping. Second, as a complementary approach to T-jumps, nanosecond transient pH-jump methods based on photoacids are developed for transient 2D IR studies of protonation-triggered protein conformational changes. Finally, the research group is continuing their ongoing development of 2D IR to study conformational changes to membrane proteins and lipid bilayers.

该奖项支持Andrei Tokmakoff教授的研究工作，旨在开发二维红外光谱（2D IR）的实验方法，以可视化DNA和蛋白质如何在真实的时间内改变其结构。尽管这些过程在材料化学、生物医学研究和纳米技术中非常重要，但目前很少有实验能够研究大分子在化学反应和物理过程中如何改变其结构，因为它们在溶液中发生在纳秒到微秒的时间尺度上。 这项工作支持两名研究生，因为他们了解溶液相化学动力学，大分子结构，蛋白质和DNA构象变化。此外，该基金还支持两本不断扩展的在线教科书，“时间依赖量子力学和光谱学”和“生物物理化学概念”。该基金的具体科学目标是继续瞬态二维红外光谱学的持续发展。 目前的方法使用的温度跳跃（T-跳跃），以启动蛋白质和DNA的构象变化，并跟踪由此产生的分子结构的变化与二维IR。首先，T-跳跃瞬态二维IR实验用于研究DNA寡核苷酸的构象动力学，包括杂交，起泡，磨损，和碱基翻转。其次，作为一种补充的方法，T-跳跃，纳秒瞬态pH跳跃方法的基础上光酸的质子化引发的蛋白质构象变化的瞬态二维红外研究。 最后，研究小组正在继续他们正在进行的2D IR的开发，以研究膜蛋白和脂质双层的构象变化。