CAREER: Thioamides as Minimalist Chromophores to Monitor Protein Dynamics

生命科学化学计划资助宾夕法尼亚大学的E.James Petersson教授获得职业奖项，以开展题为“硫代酰胺作为最低限度的生色团来监测蛋白质动力学”的研究。这个项目涉及对蛋白质运动的分子细节的研究。该研究计划的目标是开发新型的“非侵入性”探针，用于监测蛋白质结构的变化，提高结构分辨率。一个长期目标是创建实验约束的蛋白质运动的分子动力学轨迹(基本上是原子尺度的电影)。探针本身由连接蛋白质中每一种氨基酸的酰胺键的单原子O-to-S取代组成。这些探测器的尺寸非常小，因此与目前的许多探测器不同，它们不会干扰它们本应研究的运动。一旦完全开发，这个探测器就有可能提供关于蛋白质中单个氨基酸运动的详细的、时间分辨的信息。理解由大量非共价相互作用引起的协同变化不仅是生物化学的问题，而且是几乎所有纳米尺度的科学研究的问题。在开发用于运动学研究的硫代酰胺的过程中，人们将对这个相对未知的官能团在电子和物理性质方面有更多的了解。蛋白质中的结构重排通常对细胞信号和疾病中的蛋白质错误折叠很重要。硫代酰胺探针对生物界任何希望研究蛋白质运动的成员都是有用的，并可能提高生物界从基本原理设计分子马达的能力。这项工作的更广泛影响包括在多学科实验室环境中培训本科生和研究生，该环境利用有机合成、物理化学、分子和细胞生物学来研究生物现象。这笔赠款支持的其他活动包括创建一个未来学院计划，帮助培养有学术抱负的学生和博士后学者。该中心积极参与针对中学生的教育推广活动，中学生是一个经常获得和失去科学兴趣的年龄段。指导学生成为初出茅庐的研究科学家的方式是让学生参与实验的设计和结果的发布。作为初出茅庐的教师，他们通过参与校内和校外的教育活动来指导他们。这个项目得到了分子和细胞生物科学部生物分子动力学、结构和功能集群的共同资助。

The Chemistry of Life Sciences Program funds Professor E. James Petersson of the University of Pennsylvania for a CAREER award to carry out research entitled "Thioamides as Minimalist Chromophores to Monitor Protein Dynamics." This project involves the study the molecular details of protein motions. The goal of the research program is to develop novel, "non-invasive" probes that will be used to monitor changes in protein structure with increased levels of structural resolution. A long-term goal is to create experimentally-constrained molecular dynamics trajectories (essentially atomic-scale movies) of protein motions. The probes themselves consist of single-atom O-to-S substitutions to the amide bond that links every amino acid in a protein. The probes have a very small size, so that unlike many current probes, they will not perturb the motion they are meant to study. Once fully developed, this probe has the potential to provide detailed, time-resolved information on the motions of individual amino acids in the protein. Understanding concerted changes resulting from large numbers of non-covalent interactions is a problem not only for Biochemistry, but for nearly all scientific study at the nanometer scale. In the course of developing thioamides for motional studies, a greater understanding of this relatively unexplored functional group will be obtained, with regard to both electronic and physical properties.Structural rearrangements in proteins are often important to cell signaling and protein misfolding in disease. Thioamide probes can be of utility to any member of the biological community wishing to study protein motion and may improve community's ability to design molecular motors from first principles. The broader impacts of this work include training undergraduate and graduate students in a multidisciplinary laboratory environment that makes use of organic synthesis, physical chemistry, molecular, and cellular biology to investigate biological phenomena. Other activities supported by this grant include the creation of a Future Faculty program to help to train students and postdoctoral scholars with academic aspirations. The is actively engaged in educational outreach activities targeted toward middle school students, an age group where scientific interest is often gained and lost. Mentoring students as budding research scientists occurs by engaging students in the design of experiments and publication of results. Mentoring them as budding teachers occurs through their involvement in intramural and extramural educational activities. This project is receiving co-funding from the Biomolecular Dynamics, Structure and Function Cluster in the Division of Molecular and Cellular Biosciences.