CAREER: Binding and Biomolecular Dynamics in Undergraduate Teaching and Education

该奖项由2009年美国复苏和再投资法案(公法111-5)资助。该职业奖项支持一项旨在探索蛋白质折叠和功能如何依赖结构灵活性的实验研究计划。蛋白质的三维结构通过弱的非共价相互作用网络连接在一起，即使是最小的结合伙伴也可以引起结构变化。这个项目将使用这样的扰动来揭示蛋白质稳定网络的分子力学。细菌铜伴侣CusF众所周知的配体诱导的结构和动态变化将被用来阐明构象变化是如何在蛋白质的整个结构中传播的。这个项目还将展示蛋白质折叠机制如何依赖于相同的结构细节。对一组全面的CusF突变体的动力学测量将使我们能够分析稳定网络的每个成员在蛋白质折叠反应中所起的作用。最终，该项目将专注于如何使用结合伙伴来控制蛋白质结构。CusF将被重新设计，使其折叠和寡聚完全依赖于配体。这些发现不仅将为蛋白质结构、功能和设计原理提供信息，还将测试和推进蛋白质工程科学。广泛的影响：该项目超越了研究生们在大学经常经历的传统的一对一指导，以两种新颖的方式将科学研究融入到本科学习的结构中。首先，在核心课程和选修课程中，实际的研究问题都被引入了PI机构的教学实验室。从蛋白质表达和纯化到配体结合和蛋白质稳定性测量，物理化学和生物化学实验室课程的学生将通过为项目研究目标服务的活动获得解决科学问题的基本技能。这些课程将扩大该奖项涉及的学生数量，远远超过那些在研究实验室工作的学生，并将使研究经验成为每个化学专业教育经验的一部分。其次，该项目提供了一个针对社区中代表性不足的人群的外展计划；该计划将在学生职业生涯的形成时刻向他们介绍科学。通过将高中生和他们的老师带到研究实验室进行密集的暑期培训计划，该项目将增加STEM领域进入大学的学生数量，特别是来自文图拉县庞大的拉美裔社区的学生。这些学生将在进入大学时清楚地了解科学研究和发现的重要性；在这个项目中开发的独特的实验室课程将在学生随后的大学教育中加强这些知识。

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).This CAREER award supports an experimental research program aimed at exploring how protein fold and function depend on structural flexibility. Protein three-dimensional structures are held together via a network of weak non-covalent interactions, and even the smallest of binding partners can induce structural changes. This project will use such perturbations to reveal the molecular mechanics of protein stability networks. The bacterial copper chaperone CusF's well-known ligand-induced structural and dynamic changes will be used to elucidate how conformational changes are propagated throughout a protein's architecture. This project will also show how a protein folding mechanism depends on the same structural details. Kinetics measurements of a comprehensive set of CusF mutants will allow analysis of the role played by each member of the stability network in the protein folding reaction. Ultimately, the project will focus on how binding partners can be used to control protein structure. CusF will be re-engineered to make its folding and oligomerization entirely ligand-dependent. These discoveries will not only inform on protein structure, function and design principles, but will also test and advance the science of protein engineering.Broader Impacts: Moving beyond the traditional one-on-one mentoring that research students often experience in college, this project builds scientific research into the very fabric of undergraduate learning in two novel ways. First, actual research problems are being introduced into teaching laboratories at the PI's institution in both core and elective courses. From protein expression and purification to ligand-binding and protein stability measurements, students in physical chemistry and biochemistry laboratory courses will acquire the basic skills of scientific problem-solving through activities that serve the project's research objectives. These courses will broaden the number of students reached by the award far beyond those working in the research laboratory and will make the research experience a part of the educational experience of every chemistry major. Second, the project provides for an outreach program aimed at the community's underrepresented populations; this program will introduce students to science at a formative moment of their careers. By bringing high school students and their teachers into the research laboratory for an intensive summer training program, the project will increase the numbers of students entering college in the STEM fields in general, in particular, from the Ventura County's large Hispanic community. These students will begin college with a clear understanding of the importance of research and discovery in the sciences; the unique laboratory courses developed in this project will reinforce this knowledge throughout the students' subsequent college education.