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

酶催化的化学反应对工业应用、能量转换过程和生命至关重要。更好地理解酶如何进行这些化学反应将对许多科学学科产生重大影响。特别是，更深入地了解酶如何改变其三维形状是理解这一点的关键，然而，即使是最好的表征酶，其分子运动的基本细节仍然只是粗略地了解。在这个项目中，这些运动的特点和它们在酶催化功能中的作用将通过实验和计算技术的有力结合来阐明。这些实验将被应用到模型酶，磷酸丙糖异构酶（TIM），不仅将提供一个更好的理解TIM酶的功能，但也将提供有关酶的重要信息一般，将有助于在无数的相关科学领域的研究。这项研究的目标是对重要问题进行杰出的科学研究，并培养年轻科学家从各种实验角度攻击这个和其他科学问题，并挑战他们找到创造性的解决方案。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，包括相关科学文献的详细研究，在基本的生物物理概念的教育。(b)研究指导。本科生和研究生将在科学研究方面得到指导。该项目的一个特别重点是招募来自地理代表性不足的阿巴拉契亚农村的本科生参加这个研究项目。通过吸收来自地域代表性不足地区的学生，该项目将增加他们的教育经验，并扩大对那些通常没有这种机会的人的培训。(c)促进群体互动。通常，科学问题需要多种方法来实现解决方案。为了鼓励学生整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，每周将与侧重于计算方法的研究小组举行联合小组会议。

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.