CAREER:Biomolecular Flexibility: Facile Characterization of Equilibrium and Dynamical Behavior

生物分子，如蛋白质，是具有明确形状的大分子。这些形状必须改变，以便生物分子执行其生物任务。如果一个生物分子是柔韧的，它可以很容易地改变它的形状。如果它太硬，形状就不容易改变，这就会干扰生物分子的功能。蛋白质灵活性变化的原因可能包括与另一种生物分子的结合、环境的变化（如含水量或温度）以及生物分子化学成分的突变。能够快速测量生物分子的柔韧性是很重要的。目前建立的测量生物分子柔韧性的方法既耗时又需要特殊的设备。我们发现，当我们改变蛋白质的柔韧性时，在太赫兹（1012赫兹）频率范围内的光下，它们会出现不同的变化。太赫兹频率范围刚好高于移动电话的工作频率。最近，在这些频率下工作的紧凑测量系统已经开发出来，因此我们在这项工作中的目标是建立一种新的测量技术，所有研究人员都可以使用，并允许快速评估蛋白质的灵活性。此外，我们打算将这种技术应用于理解信号转导的机制。桌面柔韧性表征工具的开发将有助于蛋白质组学研究和药物设计的快速发展。该项目包括一个外展部分，旨在1)让公众了解好的科学和坏的科学，以及如何区分它们；2)通过不同种族和经济背景的年轻女性的演讲，改变公众对科学家的先入之见。该奖项由数学和物理科学理事会的物理和化学部门以及生物科学理事会的分子和细胞生物科学部共同资助。

Biomolecules, such as proteins, are large molecules with well defined shapes. These shapes must change in order for the biomolecule to perform its biological tasks. If a biomolecule is flexible, it can easily change its shape. If it is too rigid, the shape can not easily change, and this can interfere with the biomolecule's function. Reasons for protein flexibility to change can include binding of another biomolecule, changes in environment such as water content or temperature and mutations in the biomolecule's chemical composition. It is important to be able to rapidly measure a biomolecule's flexibility. Currently established methods to measure biomolecular flexibility are time consuming and require special facilities. We have found that when we do something to change the flexibility of proteins they appear different when examined with light that is in the terahertz (1012 Hz) frequency range. The terahertz frequency range is just above the frequencies at which cellular phones operate. Recently compact measurement systems working at these frequencies have been developed, thus our aim in this work is to establish a new measurement technique that can be accessible to all researchers and allows rapid assessment of protein flexibility. In addition we intend to apply this technique towards understanding mechanisms of signal transduction. The development of a table-top flexibility characterization tool will assist in rapid advances in proteomic research and drug design. The program includes an outreach component which aims to 1) expose the general public to good science, bad science and how to tell the difference and 2) change public preconceptions of who scientists are by having presentations made by young women of a variety of ethnic and economic backgrounds. This award is co-funded by the Divisions of Physics and Chemistry in the Mathematical and Physical Sciences Directorate and by the Division of Molecular and Cellular Biosciences in the Directorate for Biological Sciences.