Nonequilibrium, Single-Molecule Studies of Protein Unfolding

蛋白质展开的非平衡、单分子研究

• 批准号: 0505814
• 负责人: Ching-Hwa Kiang
• 金额: $ 30万
• 依托单位: William Marsh Rice University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0505814&HistoricalAwards=false
• 关键词: Nonequilibrium; Single; Molecule; Studies; Protein

***NON-TECHNICAL ABSTRACT***An accurate knowledge of the energy difference between equilibrium states of protein systems is important for biophysical and biochemical understanding of molecular processes. This award will support a project focused on developing effective techniques to study this energy difference, or protein stability, at the molecular level. The studies will aid our understanding of protein stability, and ultimately our understanding of the role of protein stability in proper functioning under physiological conditions. Atomic force spectroscopy is a technique used to measure the behavior of molecules under a stretching or twisting force. Application of this technique to important molecules such as human cardiac titin will lead to understanding of how the muscle functions in heart. A new course on molecular biophysics will be developed. Students and postdoctoral associates will have the opportunity to learn to use the state-of-the art instrument for biophysics research. This project receives support from the Division of Materials Research and the Physics Division.***TECHNICAL ABSTRACT***This individual investigator award will support single-molecule studies of protein free energy landscapes by dynamic force spectroscopy using atomic force microscopy. The goal is to obtain equilibrium information about nanoscale biomolecular systems from non-equilibrium measurements. State-of-the art atomic force microscopy capable of manipulating single molecules at the nanometer scale and detecting forces with pico-newton accuracy will be used to measure the force-extension of single proteins. The recently derived Jarzynski equality, which relates the probability distribution of nonequilibrium work values to the equilibrium free energy difference, will be used to determine the free energy changes as proteins undergo mechanical transformations. The unfolding free energy curves of titin, the giant muscle protein responsible for the passive tension of heart muscles, will be obtained using Jarzynski's equality. The broader impact of this program includes the development of a novel measurement and analysis tool for solving basic biophysical problems and the training of undergraduate students, graduate students, and postdoctoral associates in nanobiophysics. This project receives support from the Division of Materials Research and the Physics Division.

*非技术摘要*对蛋白质系统平衡状态之间的能量差的准确了解对于分子过程的生物物理和生物化学理解是重要的。该奖项将支持一个项目，该项目专注于开发有效的技术，在分子水平上研究这种能量差异或蛋白质稳定性。这些研究将有助于我们理解蛋白质的稳定性，并最终帮助我们理解蛋白质稳定性在生理条件下正常运作中的作用。原子力光谱是一种用来测量分子在拉伸或扭转力作用下的行为的技术。将这项技术应用于人类心脏肌动蛋白等重要分子，将有助于理解肌肉在心脏中的功能。将开发一门关于分子生物物理学的新课程。学生和博士后助理将有机会学习使用最先进的仪器进行生物物理学研究。该项目得到了材料研究部和物理部的支持。*技术摘要*这一个人研究人员奖将支持利用原子力显微镜的动态力光谱学对蛋白质自由能景观的单分子研究。目标是从非平衡测量中获得有关纳米级生物分子系统的平衡信息。最先进的原子力显微镜能够在纳米尺度上操纵单分子，并以皮牛顿的精度检测力，将被用于测量单个蛋白质的力延伸。最近推导出的Jarzynski等式，将非平衡功的概率分布与平衡自由能差联系起来，将被用来确定蛋白质经历机械转换时的自由能变化。肌动蛋白是一种引起心肌被动张力的巨大肌肉蛋白，其展开的自由能曲线将由雅津斯基公式得到。该计划的更广泛影响包括开发一种新的测量和分析工具来解决基本的生物物理问题，以及培训本科生、研究生和博士后在纳米生物物理学方面的助理。该项目得到了材料研究部和物理部的支持。