Single Molecule Studies of Protein Folding

蛋白质折叠的单分子研究

• 批准号: 1122225
• 负责人: Susan Marqusee
• 金额: $ 117.85万
• 依托单位: University of California-Berkeley
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2017-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1122225&HistoricalAwards=false
• 关键词: Single; Molecule; Studies; Protein; Folding

The objective of this project is to investigate the protein-folding problem using single molecule studies. Protein folding, the mechanism by which the amino acid sequence directs the energy landscape of a protein (the structures, energies, and rates of interconversion of all of the accessible conformations), remains a major challenge for modern molecular biology. Without a better understanding of how these features are encoded in a protein sequence, the expanding sequence databases continue to conceal the answers to many important questions. The project aims to develop methods for applying force or tension on a single protein molecule using tools such as an optical trap or magnetic tweezers and monitoring the conformation of the protein by following the distance between specific sites in the protein. The results will yield observables that can be used directly in theoretical studies of protein folding and the design of the experiments will be carried out in an iterative collaboration with theoreticians in the field. Mechanical stress plays a ubiquitous role in protein function and biology, and therefore, in addition to providing needed insight into the protein-folding problem this work will also provide much needed information about the mechanical stability of proteins.In addition to its impact in protein folding and macromolecular biophysics, the research in this project requires training at the intersection of physics and biology: the work is a collaborative effort between a physics and a biochemistry lab. The work is not just interdisciplinary; it is actually interdependent, requiring state-of-the-art experiments in both physics and molecular biology. The work requires a combination of students and postdoctoral trainees with diverse backgrounds to work closely together. The project also involves the help of undergraduates, particularly those with a background in engineering and physics, giving them direct exposure to the biological sciences. In sum, this work offers a unique educational experience for the students and post-doctoral fellows involved in the project, and will help to train a new generation of scientists fluent in both the biological and quantitative sciences.

该项目的目的是使用单分子研究研究蛋白质折叠问题。蛋白质折叠，氨基酸序列指导蛋白质的能量景观的机制（所有可访问构象的结构，能量和互转换的速率）仍然是现代分子生物学的主要挑战。如果没有更好地了解这些特征是如何以蛋白质序列编码的，则扩展的序列数据库继续隐瞒了许多重要问题的答案。该项目旨在使用诸如光学陷阱或磁镊子等工具在单个蛋白质分子上施加力或张力的方法，并通过遵循蛋白质中特定位点之间的距离来监测蛋白质的构象。结果将产生可观察到的可观察物，可以直接在蛋白质折叠的理论研究中使用，并且实验的设计将与该领域的理论家进行迭代合作进行。机械压力在蛋白质功能和生物学中发挥着无处不在的作用，因此，除了提供对蛋白质折叠问题所需的见解外，此工作还将提供有关蛋白质的机械稳定性的急需信息。在其对蛋白质折叠和蛋白质折叠的影响和巨粒分子生物物理学的影响外，该项目在该项目中还需要一定的物理学和物理学的研究：一定的物理学：一定的工作：一定的工作：一定的工作：一定的工作：一定的工作：一定的工作：一定的工作：一定的一项物理学：一定的工作：一定的一项物理学的研究：一定的工作：一项物理学的研究：一定的物理学和一项工作。生物化学实验室。这项工作不仅是跨学科的；它实际上是相互依存的，需要在物理和分子生物学上进行最新的实验。这项工作需要组合学生和具有不同背景的博士后学员，才能紧密合作。该项目还涉及本科生的帮助，尤其是那些具有工程和物理学背景的人，使他们直接接触生物科学。总而言之，这项工作为参与该项目的学生和博士后研究员提供了独特的教育经验，并将有助于培训新一代的科学家流利的生物学和定量科学。