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.

理解生命规则的一个根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理解。该项目将提供有关氨基酸序列和环境如何调节蛋白质能量景观的生物物理信息，蛋白质结构或构象与控制其稳定性的热力学性质之间的映射。氨基酸序列、环境和能量景观之间的这种联系对于设计具有目标行为（如功能、机械特性和寿命）的蛋白质的能力至关重要。此外，PI将制定一项计划，为加州大学伯克利分校生命科学领域的研究生和博士后提供广泛的职业接触，探索和经验。 将设立一个新的专业人员居住（PIR）计划，来自不同领域的专业人员将在该计划中工作。（工业和创业，教育和推广，政策和通信，学术和研究机构）将花几天，每年在加州大学伯克利分校与学员和教师互动-让他们接触到来自不同职业道路的成功专业人士。这项研究的科学目标是调查蛋白质-折叠问题使用单分子力学研究和氢交换技术。这项工作的结果将进一步加深我们对蛋白质折叠的理解，蛋白质折叠是氨基酸序列指导蛋白质能量景观的机制（所有可接近构象的结构，能量和相互转化率），这是现代分子生物学的主要挑战。如果没有更好地理解这些特征是如何在蛋白质序列中编码的，不断扩大的序列数据库将继续掩盖许多重要问题的答案。单分子蛋白质折叠研究的结果将产生可直接用于蛋白质折叠理论研究的可观测值，实验将与该领域的理论家进行迭代合作。机械应力在蛋白质功能和生物学中起着普遍的作用，因此，除了提供必要的洞察蛋白质折叠问题，这项工作也将提供急需的信息，关于蛋白质的机械稳定性。本项目由分子和细胞生物科学部的分子生物物理学集群和物理部的生命系统计划的物理学共同资助。