The energy landscape for folding and function of biomolecules: integrating physical models, genetic information and experiments

生物分子折叠和功能的能量景观：整合物理模型、遗传信息和实验

• 批准号: 1614101
• 负责人: Jose Onuchic
• 金额: $ 139.08万
• 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: 2016
• 资助国家: 美国
• 起止时间: 2016-09-15 至 2023-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1614101&HistoricalAwards=false
• 关键词: energy; landscape; folding; function; biomolecules

This project is jointly funded by the Molecular Biophysics Cluster in the Division of Molecular and Cellular Biosciences, the Physics of Living Systems in the Division of Physics and the Chemistry of Life Processes Program in the Division of Chemistry.The life of cells is orchestrated by a network of chemical reactions involving numerous proteins and nucleic acids, and the transport of these molecules between cellular compartments. The research supported by this award focuses on the structure-function relationship of biomolecules, focusing mostly on proteins but also with extensions to nucleic acids. Using the power of theoretical approaches, this project investigates how proteins distribute their energy between structure and function. The project also explores the three-dimensional organization of the genome by creating new physical models for chromatin organization. The theoretical work may be used to guide and influence the research in folding and function in both theoretical and experimental communities. This research provides training for students and postdoctoral fellows in the highly interdisciplinary field of molecular biophysics.Structure based models (SBMs) have been shown to be a useful tool for understanding the global geometrical features governing folding. Grounded on energy landscape theory (ELT) and the funnel concept, these models are supported by the fact that most naturally occurring proteins have sufficiently reduced energetic frustration. Structure-based models are limited by the availability of structural information, particularly those pertaining to all the different functional configurations. Direct Coupling Analysis (DCA) may predict amino acid contacts in proteins. The research is based on SBMs supplemented by DCA information and integrated with explicit solvent all-atom simulations. The project focuses on proteins and several biomolecular machines. Finally, inspired by the early successes of this approach to proteins and other molecular machines, an important goal of this project deals with chromosome folding and function.

该项目由分子和细胞生物科学部的分子生物物理学组、物理学部的生命系统物理学和化学部的生命过程化学项目共同资助。细胞的生命是由涉及大量蛋白质和核酸的化学反应网络以及这些分子在细胞区室之间的运输所协调的。该奖项支持的研究重点是生物分子的结构-功能关系，主要集中在蛋白质上，但也扩展到核酸。利用理论方法的力量，该项目研究蛋白质如何在结构和功能之间分配能量。该项目还通过创建染色质组织的新物理模型来探索基因组的三维组织。 这些理论工作可以用来指导和影响理论界和实验界对折叠和功能的研究。这项研究为学生和博士后研究员提供了培训，在高度跨学科领域的分子生物physics.Structure为基础的模型（SBMs）已被证明是一个有用的工具，了解全球的几何特征的折叠。基于能量景观理论（ELT）和漏斗概念，这些模型得到了大多数天然蛋白质充分减少能量挫折的事实的支持。 基于结构的模型受到结构信息可用性的限制，特别是那些与所有不同功能配置有关的信息。直接偶联分析（DCA）可以预测蛋白质中的氨基酸接触。该研究是基于补充DCA信息的SBM，并与显式溶剂全原子模拟相结合。该项目的重点是蛋白质和几种生物分子机器。最后，受这种方法在蛋白质和其他分子机器方面的早期成功的启发，该项目的一个重要目标是染色体折叠和功能。