Two-Dimensional Infrared Spectroscopy of the Conformational Dynamics of Biomolecules

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和蛋白质如何实时改变其结构。尽管这些过程在材料化学、生物医学研究和纳米技术中很重要，但目前很少有实验能够研究在化学反应和物理过程中大分子如何改变其结构，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学习溶液相化学动力学，大分子结构，蛋白质和DNA构象变化。此外，该基金还将支持两本不断扩展的在线教科书，《时变量子力学与光谱学》和《生物物理化学概念》。这项拨款的具体科学目标是继续正在进行的瞬态二维红外光谱的发展。目前的方法使用温度跳变（t跳）来引发蛋白质和DNA的构象变化，并使用二维红外跟踪分子结构的变化。首先，利用t跃迁瞬态二维红外实验研究DNA寡核苷酸的构象动力学，包括杂交、冒泡、磨损和碱基翻转。其次，作为t跃迁的补充方法，基于光酸的纳秒瞬态ph跃迁方法被开发用于质子触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研究膜蛋白和脂质双分子层的构象变化。

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.