CAREER: Disorder, tRNA composition and energy transduction in the ribosome

该项目由生物科学理事会分子与细胞生物科学部的分子生物物理学和数学与物理科学理事会物理部的生命系统物理学项目共同支持，其目标是利用模拟来确定生物分子机器将化学能转化为机械能的方式。特别是，该项目旨在揭示如何利用无序来提高细胞的效率和准确性。我们感兴趣的分子系统是核糖体，这是一种负责构建蛋白质的大型复合体。在核糖体内部，大规模的构象重排促进了化学和机械步骤之间的能量转移。为了确定这些步骤的分子起源，该项目将研究作为核糖体“引擎”的分子延伸因子的动力学。通过识别这些分子的功能特性，这些研究将揭示控制生物功能的物理原理。该项目将在当地和国际层面产生社会影响。这项工作将吸引来自代表性不足群体的本科生，并使他们接触到生命科学和物理科学领域的各种主题。作为研究小组的成员，这些学生将与科学界紧密结合，有机会在会议和其他公共场所展示他们的工作。此外，本项目中使用的方法将被纳入本科课程，这将逐渐灌输对基础科学教育与现实世界研究之间联系的理解。该项目还将为更广泛的科学界提供全国范围的分子建模培训讲习班。这将使受训者能够在设计更精确的实验研究时应用理论方法。在国际上，该项目将通过与巴西的直接科学合作，促进国外生物物理学研究的发展。此外，这些合作将使美国学生沉浸在国际研究环境中，丰富他们的科学和文化经验。这将使他们有机会发展一个全球同事网络，这将帮助他们成为国际公认的科学领袖。

The goal of this project, which is jointly supported by Molecular Biophysics in the Division of Molecular and Cellular Biosciences in the Directorate for Biological Sciences and the Physics of Living Systems Program in the Division of Physics in the Mathematical and Physical Sciences Directorate, is to employ simulations to identify ways that biomolecular machines convert chemical energy into mechanical work. In particular, this project seeks to reveal how disorder is utilized to increase efficiency and accuracy in the cell. The molecular system of interest is the ribosome, a large complex responsible for building proteins. Within the ribosome, large-scale conformational rearrangements facilitate the transfer of energy between chemical and mechanical steps. To identify the molecular origins of these steps, this project will investigate the dynamics of Elongation Factors, the molecules that serve as the ribosome's "engine." By identifying the functional properties of these molecules, these studies will reveal the physical principles that control biological function.This project will have societal impacts, at both the local and international level. This work will engage undergraduate students from underrepresented groups and expose them to a diverse range of topics in the life sciences and physical sciences. As members of the research team, these students will be tightly integrated within the scientific community, having opportunities to present their work at conferences and other public venues. Additionally, the methods used in this project will be incorporated within the undergraduate curriculum, which will instill an understanding of the connection between basic science education and real-world research. This project will also provide nationally-accessible training workshops in molecular modeling to the broader scientific community. This will enable trainees to apply theoretical approaches when designing more-precise experimental studies. Internationally, this project will contribute to the growth of biophysics research abroad through direct scientific collaborations with Brazil. Further, these collaborations will enrich the scientific and cultural experience of students in the US by immersing them in an international research environment. This will give them opportunities to develop a global network of colleagues, which will help them become internationally recognized scientific leaders.