Conformational Dynamics and the Energy Landscape of Calmodulin

在该奖项中，由化学部的实验物理化学计划和生物局分子和细胞生物科学部的分子生物物理学计划资助，堪萨斯大学的Carey Johnson教授和John P.Ralston教授以及他们的研究生和本科生同事将开发先进的单分子荧光相关光谱技术，用于研究钙信号蛋白钙调蛋白的长时间(微秒级)构象动力学。这些研究的目标是同时研究具有生物重要性的蛋白质的构象动力学，同时开发先进的生物物理技术，可以被其他研究人员应用于蛋白质动力学的其他问题。蛋白质中的一些重要的动力学过程需要几毫秒的时间才能发生。对于大多数理论和实验技术来说，这是一个有问题的时间范围--对于希望了解蛋白质在生物系统中如何工作的物理学家来说，科学工具箱中缺少一个工具。教授们。约翰逊、拉尔斯顿和他们的学生合作者希望开发这个工具。在此过程中，他们将试图解开一种重要的钙结合蛋白-钙调蛋白的内部工作原理，它的功能是一个分子开关，因为它对钙离子信号做出反应，并在许多生物途径中激活目标酶。这项研究是跨学科的，将为从事这项研究的学生提供物理和生物科学方面的独特技能。此外，参与该项目的本科生将从堪萨斯大学和哈斯克尔印第安人民族大学桥梁项目中招聘。在该项目过程中开发的单分子分析软件将通过一个网站广泛传播。

In this award, funded by the Experimental Physical Chemistry Program of the Chemistry Division and the Molecular Biophysics Program of the Molecular and Cellular Biosciences Division of the Biology Directorate, Prof. Carey Johnson and Prof. John P. Ralston of the University of Kansas and their graduate and undergraduate student colleagues will develop advanced single-molecule fluorescence correlation spectroscopy techniques for studying the long-time (microsecond - millisecond) conformational dynamics of Calmodulin -- a calcium signaling protein. The goals of these studies are to simultaneously study the conformational dynamics of a biologically important protein whilst developing advanced biophysical techniques that can be applied by other researchers to other problems in protein dynamics.Some important dynamical processes in proteins take up to milliseconds to occur. This is a problematical time range for most theoretical and experimental techniques -- there is a missing tool in the scientific toolbox for physical scientists who wish to understand how proteins work in biological systems. Profs. Johnson, Ralston and their student collaborators wish to develop this tool. In the course of doing this, they will try to unravel the inner workings of an important calcium binding protein, Calmodulin, which functions as a molecular switch, as it responds to calcium ion signals and activates target enzymes in a number of biological pathways. The research is interdisciplinary, and will provide the students working on it with unique skills in the physical and biological sciences. In addition, the undergraduates working on this project will be recruited from the University of Kansas and Haskell Indian Nations University Bridge Project. The single-molecule analysis software developed over the course of this project will be broadly disseminated via a website.