CAREER: Understanding Protein Folding Dynamics in the Ultra-Fast Limit

职业：了解超快极限下的蛋白质折叠动力学

• 批准号: 0347124
• 负责人: Stephen Hagen
• 金额: --
• 依托单位: University of Florida
• 依托单位国家: 美国
• 项目类别: Continuing grant
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0347124&HistoricalAwards=false
• 关键词: CAREER; Understanding; Protein; Folding; Dynamics

This project will investigate some of the unique phenomena associated with protein folding and assembly on very fast time scales. Nanosecond and microsecond events in protein folding can now be probed by experimentalists using laser spectroscopy, and by theorists using state-of-the-art molecular dynamics simulation. Because many small, newly-designed proteins and peptides fold rapidly, ultra-fast folding is the regime where the experimental, theoretical, and design aspects of protein folding all converge. However, it is also a regime that strains the assumptions and interpretations behind standard physical descriptions of the protein folding problem: fast folding is different from slow folding. This project applies time-resolved laser spectroscopy to small, designed proteins and peptides in order to examine the limits of standard barrier-crossing descriptions of folding, and to investigate how the assumptions behind those descriptions may break down for the very fastest folding molecules. It focuses on (1) the meaning of reaction friction in Kramers models for folding, (2) the speed of rapid reorganizations of unfolded polypeptides, and (3) the deviation from simple barrier-crossing kinetics that is expected for ultrafast folding.The broader impact of this project derives in part from its advancement of basic understanding of the limits of simple physical models for complex biochemical phenomena, and from the fact that it supports time-resolved spectroscopic instrumentation that enhances the scientific research infrastructure in molecular biophysics. A broader impact also derives the educational components of the plan. The PI will lead a K-12 outreach effort aimed at a local middle school that has a large minority enrollment and substantial numbers of disadvantaged students. The project aims to motivate and support the participation of more of these students in the optional science fair by providing them with regular mentoring over a period of many weeks as they undertake their science fair projects. The plan also provides for research laboratory teaching and training for undergraduate and graduate students in interdisciplinary biological physics: This training initiates physical-science students into the study of biological systems, and it introduces biologically-inclined students to physical instrumentation and methodologies. This project is jointly funded by the Molecular Biophysics Program in the Division of Molecular and Cellular Biosciences and the Division of Physics in the Mathematical and Physical Sciences Directorate.

这个项目将研究一些与蛋白质折叠和组装在非常快的时间尺度上的独特现象。 蛋白质折叠中的纳秒和微秒事件现在可以由实验学家使用激光光谱学来探测，也可以由理论家使用最先进的分子动力学模拟来探测。 由于许多新设计的小蛋白质和肽快速折叠，超快折叠是蛋白质折叠的实验，理论和设计方面都会聚的区域。 然而，这也是一个制度，应变的假设和解释背后的标准物理描述的蛋白质折叠问题：快速折叠是不同的缓慢折叠。 该项目将时间分辨激光光谱应用于小的，设计的蛋白质和肽，以检查折叠的标准障碍交叉描述的限制，并研究这些描述背后的假设如何打破最快折叠分子。 它的重点是（1）Kramers折叠模型中反应摩擦的意义，（2）未折叠多肽快速重组的速度，（3）超快折叠所预期的简单跨越障碍动力学的偏离。该项目的广泛影响部分来自于它对复杂生物化学现象的简单物理模型的局限性的基本理解的进步，以及它支持时间分辨光谱仪器的事实，这增强了分子生物物理学的科学研究基础设施。 更广泛的影响还来自该计划的教育部分。 PI将领导一项针对当地一所中学的K-12外展工作，该中学拥有大量少数民族入学人数和大量弱势学生。 该项目旨在激励和支持更多的学生参加可选的科学博览会，在他们进行科学博览会项目时，为他们提供为期数周的定期指导。 该计划还为跨学科生物物理学的本科生和研究生提供研究实验室教学和培训：这种培训使物理科学学生开始研究生物系统，并向生物学倾向的学生介绍物理仪器和方法。该项目由分子和细胞生物科学部的分子生物物理学计划以及数学和物理科学理事会的物理学部共同资助。