Single Molecule Studies of Protein Folding

蛋白质折叠的单分子研究

• 批准号: 1616591
• 负责人: Susan Marqusee
• 金额: $ 142.48万
• 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: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1616591&HistoricalAwards=false
• 关键词: Single; Molecule; Studies; Protein; Folding

A fundamental obstacle to understanding the rules of Life, is the lack of a predictive, molecular understanding of the mechanisms by which the genome encodes the function of a protein. This project will provide biophysical information on how the amino acid sequence and the environment tune a protein's energy landscape, the mapping between protein structure or conformation and thermodynamic properties which govern its stability. This connection between amino acid sequence, environment and energy landscape is imperative for the ability to design proteins with targeted behaviors such as function, mechanical properties, and lifetime. In addition, the PI will develop a program to provide broad career exposure, exploration and experience to graduate students and postdocs in the life sciences at UC Berkeley. A novel Professionals in Residence (PIR) program will be instituted, where professionals from diverse fields (Industry and Entrepreneurship, Education and Outreach, Policy and Communication, Academic and Research Institutes) will spend several days a year at UC Berkeley interacting with both trainees and faculty - exposing them to successful professionals from a variety of career paths.The scientific objective of this research is to investigate the protein-folding problem using single molecule mechanical studies and hydrogen exchange techniques. The results from this work will further our understanding of 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), 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 results of the single-molecule protein folding studies will yield observables that can be used directly in theoretical studies of protein folding and 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.This project is jointly funded by the Molecular Biophysics Cluster in the Division of Molecular and Cellular Biosciences and the Physics of Living Systems Program in the Division of Physics.

理解生命规则的基本障碍是缺乏对基因组编码蛋白质功能的机制的预测性，分子的理解。该项目将提供有关氨基酸序列和环境如何调整蛋白质的能量景观，蛋白质结构或构象之间的映射以及控制其稳定性的热力学特性的生物物理信息。对于具有针对性行为（例如功能，机械性能和寿命）设计蛋白质的能力，必须具有氨基酸序列，环境和能量景观之间的这种联系。此外，PI将制定一项计划，以在UC Berkeley的生命科学中为研究生和博士后提供广泛的职业曝光，探索和经验。 将制定一个新颖的居住专业人士（PIR）计划，来自不同领域的专业人员（行业和企业家精神，教育和宣传，政策和沟通，政策和沟通，学术和研究机构）将在UC Berkeley每年花几天的时间在加州大学伯克利分校与学员互动，并与他们互动，从而使他们从事研究和研究方面的杂型教学途径。交换技术。这项工作的结果将进一步理解蛋白质折叠，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，能量和互转换速率），这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。单分子蛋白折叠研究的结果将产生可观察到的物品，这些可观察到可以直接用于蛋白质折叠的研究，并且实验将在与该领域的理论家进行迭代合作中进行。机械压力在蛋白质功能和生物学中起着无处不在的作用，因此，除了提供所需的深入了解蛋白质折叠问题之外，这项工作还将提供有关蛋白质机械稳定性的急需信息。该项目由分子生物物理学集群共同资助了分子和细胞生物系统和细胞生物学的物理学的生物学和物理系统的分裂。