Biophysical Characterization of Concerted Microsecond Loop Motions and Their Role in Enzyme Catalysis

酶催化化学反应，这些化学反应对工业应用、能量转换过程和生活都是必不可少的。更好地了解酶是如何执行这些化学反应的，将对许多科学学科产生重大影响。特别是，更深入地了解酶是如何改变其三维形状的，对于这种理解是至关重要的，然而，即使在特征最好的酶中，其分子运动的基本细节也只是粗略的了解。在这个项目中，这些运动将被表征，它们在酶催化功能中的作用将通过实验和计算技术的强大组合来阐明。这些实验将应用于模型酶-磷酸丙糖异构酶(TIM)，不仅将提供更好地了解TIM酶的功能，而且还将提供有关酶的重要信息，这将有助于众多相关科学领域的研究。这项研究的目的是在重要问题上进行杰出的科学研究，并培养青年科学家从各种实验角度解决这一问题和其他科学问题，并进一步挑战他们得出创造性的解决方案。这一目标将通过三个途径实现。(A)教学。学生将通过传统的课程学习生物物理学的基本概念，包括详细学习相关的科学文献。(B)研究辅导。本科生和研究生将接受科学研究方面的指导。该项目的一个特别重点是从地理分布不足的阿巴拉契亚农村地区招募本科生参与这一研究项目。通过纳入来自人口比例偏低地区的学生，该项目将加强他们的教育经验，并扩大对那些通常不会有这种机会的人的培训。(C)促进小组互动。通常，科学问题需要多种方法来实现解决方案。为了鼓励学生综合从多个实验中获得的结果，本研究项目将促进具有不同研究背景的学生之间的互动。为此，将与侧重于计算方法的研究小组举行每周联合小组会议。

Enzymes catalyze chemical reactions that are essential for industrial applications, energy conversion processes, and life. A better understanding of how enzymes perform these chemical reactions will have a major impact on a large number of scientific disciplines. In particular, deeper insight into how enzymes change their three-dimensional shape is essential to this understanding, yet in even the best characterized enzymes, the fundamental details of their molecular motions remain only crudely understood. In this project, these motions will be characterized and their role in enzyme catalytic function will be elucidated by a powerful combination of experimental and computational techniques. These experiments will be applied to the model enzyme, triosephosphate isomerase (TIM) and will not only provide a better understanding of TIM enzyme function, but will also provide important information about enzymes in general that will aid research in a myriad of related scientific fields. The objectives of this research are to perform outstanding science on important problems and to train young scientists to attack this and other scientific problems from a variety of experimental perspectives and furthermore, to challenge them to arrive at creative solutions. This goal will be accomplished through three approaches. (a) Teaching. Students will be educated in fundamental biophysical concepts through traditional coursework that includes detailed study of relevant scientific literature. (b) Research Mentoring. Undergraduate and graduate students will be mentored in scientific research. A particular emphasis of this project focuses on recruiting undergraduates from geographically underrepresented, rural Appalachia to participate in this research project. By including students from geographically underrepresented areas this project will enhance their educational experience and expand the training for those who would not normally have such opportunities. (c) Facilitating Group Interaction. Often, scientific problems require multiple approaches to achieve a solution. To encourage students to integrate results obtained from multiple experiments, this research project will promote interactions among students with diverse research backgrounds. To this end, weekly joint group meetings with research groups that focus on computational methods will be held.