CAREER: Thioamides as Minimalist Chromophores to Monitor Protein Dynamics

生命科学计划的化学基金教授E。宾夕法尼亚大学的James Petersson获得了职业奖，以开展题为“硫代酰胺作为最低限度的发色团来监测蛋白质动力学”的研究。“这个项目涉及研究蛋白质运动的分子细节。 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。一个长期的目标是创建实验约束的分子动力学轨迹（基本上是原子尺度的电影）的蛋白质运动。 探针本身由连接蛋白质中每个氨基酸的酰胺键的单原子O到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，它们不会干扰它们要研究的运动。 一旦完全开发，这种探针有可能提供有关蛋白质中单个氨基酸运动的详细的时间分辨信息。 理解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科学研究的问题。 在发展硫代酰胺的运动研究的过程中，这个相对未开发的官能团将获得更好的理解，关于电子和物理性质。蛋白质中的结构重排通常是重要的细胞信号和疾病中的蛋白质错误折叠。 硫代酰胺探针可用于希望研究蛋白质运动的生物群体的任何成员，并且可提高群体从第一原理设计分子马达的能力。 这项工作的更广泛的影响包括在多学科实验室环境中培训本科生和研究生，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。 该补助金支持的其他活动包括创建未来教师计划，以帮助培养有学术抱负的学生和博士后学者。 该研究所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组。 通过让学生参与实验设计和结果发表，指导学生成为初露头角的研究科学家。 通过他们参与校内和校外教育活动，指导他们成为崭露头角的教师。 该项目正在接受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.