Comparison of Vibrational Coupling and Vibrational Energy Transfer Mechanisms Between Probe Pairs in Different Molecular Scaffolds to Capture Dynamic Structures via 2D IR

在化学结构、动力学和机理a （CSDM-A）项目的支持下，内华达大学里诺分校的Matthew Tucker和他的团队正在开发新的振动探针对，用于测量生物分子的结构动力学，包括RNA和蛋白质。振动标签允许研究人员以与生物活性相关的时间和结构分辨率的独特组合来监测这些分子内的运动。这些测量揭示了与离子跨细胞膜运输有关的机制细节，这一过程对人类生物学中稳态和偏离正常稳态条件具有重要意义。细胞离子运输通常取决于体内的酸水平。因此，研究人员使用激光脉冲启动pH值跳跃，然后使用振动探针对作为标签跟踪分子运动，以产生负责生物活性的分子运动的一步一步的“分子电影”。除了该项目的科学目标之外，塔克博士和他的研究小组还将通过参与美国化学学会针对经济困难高中生的SEED计划和针对第一代大学生的向上发展计划等项目，努力招募和培训来自不同背景和代表性不足的未来科学家。塔克小组还致力于开发一个系列研讨会，以鼓励参与科学、技术、工程和数学（STEM）教育和研究。该系列研讨会的目的是向家长和学生，特别是来自美国原住民社区的学生，展示科学技术如何影响他们周围的世界。本研究描述了独特的红外探针对之间的相互作用，以揭示振动耦合机制，提供对分子中热能流动的见解，并最终通过二维红外光谱捕获分子运动的结构快照。具体来说，研究小组正在使用二维红外测量来揭示涉及M2流感质子通道和离子通过Kv11.1 K+通道传输的分子运动的时间分辨结构信息。为了实现这些目标，Tucker和他的团队正在开发新的光谱探针对，可以用来同时测量各种分子支架内的距离和角度，同时也延长了探针对的振动寿命，以便在时间尺度上测量分子动力学，这是2D红外光谱很难实现的。研究小组还在努力区分探针对中的振动耦合和振动能量传递途径，以调节耦合机制并扩大距离限制。最后，该团队正在努力将这些新的光谱工具与瞬态ph跳变二维红外光谱相结合，以研究模型水和离子通道中ph依赖的质子转移和离子传输机制的反应途径。该方法有望揭示模型系统中与离子门控和质子门控相关的关键输运事件的结构动力学，其时间尺度从单键旋转周期（fs-ps）到重要构象重组所需的时间（ns-ms），采用平衡和瞬态二维红外光谱。学生培训机会和教育外展活动进一步扩大了项目的影响。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

With support from the Chemical Structure, Dynamics and Mechanisms-A (CSDM-A) Program in the Division of Chemistry, Matthew Tucker and his group at the University of Nevada-Reno are developing new pairs of vibrational probes for measuring the structural dynamics of biological molecules, including RNA and proteins. The vibrational labels allow the researchers to monitor motions within these molecules with a unique combination of temporal and structural resolution that is relevant to biological activity. The measurements reveal mechanistic details related to ion transport across cell membranes, a process that has important implications for homeostasis and deviations from normal steady state conditions in human biology. Cellular ion transport often depends on acid levels within the body. Therefore, the researchers use lasers pulses to initiate pH jumps and then track molecular motion using the vibrational probe pairs as labels to produce a step-by-step "molecular movie" of the molecular motions that are responsible for the biological activity. In addition to the scientific objectives of the project, Dr. Tucker and his research group will work to recruit and train future scientists from diverse and underrepresented backgrounds through participation in programs such as the American Chemical Society SEED program for economically disadvantaged high school students and the Upward Bound Program for first-generation college students. The Tucker group is also working to develop a seminar series to encourage participation in science, technology, engineering, and mathematics (STEM) education and research. The goal of the seminar series is to show parents and students, especially those from the Native American community, how science and technology affects the world around them.This research characterizes the interactions between unique IR (Infrared) probe pairs in order to uncover vibrational coupling mechanisms, provide insights into thermal energy flow in molecules, and ultimately capture structural snapshots of molecular motion via 2D IR spectroscopy. Specifically, the research team is using 2D IR measurements to reveal time-resolved structural information about the molecular motions involved in the M2 Influenza proton channel and ion transport through the Kv11.1 K+ channel. In order to achieve these goals, Tucker and his team are developing novel spectroscopic probe pairs that can be used to simultaneously measure distances and angles within a variety of molecular scaffolds, while also extending the vibrational lifetimes of the probe pairs in order to allow measurements of the molecular dynamics on time scales seldom achieved with 2D IR spectroscopy. The research team is also working to distinguish vibrational coupling and vibrational energy transfer pathways in the probe pairs in order to regulate the coupling mechanisms and expand distance limitations. Finally, the team is working to combine these new spectroscopic tools with transient pH-jump 2D IR spectroscopy to investigate the reactive pathways of the pH-dependent proton transfer and ion transport mechanisms within model water and ion channels. The approach holds the promise of revealing structural dynamics of key transport events related to ion gating and proton gating within model systems on time scales ranging from single bond rotational periods (fs-ps) to the times required for significant conformational reorganization (ns-ms) by employing both equilibrium and transient 2D IR spectroscopy. Student training opportunities and educational outreach activities further broaden the impact of the project.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.