CAREER: Understanding Biomolecular Recognition Involving Large Conformational Changes

职业：了解涉及大构象变化的生物分子识别

• 批准号: 0447533
• 负责人: Jin Wang
• 金额: --
• 依托单位: SUNY at Stony Brook
• 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: 2005-06-01 至 2010-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0447533&HistoricalAwards=false
• 关键词: CAREER; Understanding; Biomolecular; Recognition; Involving

Molecular recognition is one of the key issues in modern molecular biology. Although rigid and semi-rigid binding has been extensively explored, flexible binding with large conformational changes which is often found in the process and function of the cell is not well understood yet. The objective of this project, jointly supported by Molecular Biophysics in the Division of Molecular and Cellular Biosciences and the Theoretical and Computational Chemistry Program in the Chemistry Division, is to establish a theoretical framework to understand the fundamental mechanism (how flexibility might help recognition) and quantify the kinetic paths of the flexible binding. The study of the flexible binding will be carried out in three integrated steps: First, a theoretical framework for flexible binding will be established to understand the role of flexibility on the thermodynamic properties. Second, a path integral formalism will be developed to quantify the kinetic binding paths, understand the roles of flexibility and folding on the kinetics of flexible binding, and answer the questions on the fundamental mechanism of binding such as which set of kinetic paths the binding will be more likely to take. Third, the question of how the flexibility helps the recognition at the atomic level will be explored. The major intellectual merit of this research is to understand the fundamental mechanisms of flexible bio-molecular recognition through the development of a new theoretical framework and identification of kinetic paths. The principles learned can be used to guide the atomic level kinetic path simulations of specific recognition complexes, overcome the conventional computational bottleneck and explore the dynamic functions. The educational aspect of the project will have broad impact on students from all over the world pursuing interdisciplinary studies at the interface of biology/chemistry/physics, starting with the students in the U. S., China, and Brazil. The research and education efforts will be integrated. This includes designing interdisciplinary courses and curricula on bio-molecular recognition and computational biology for undergraduate and graduate students; writing a book on energy landscapes of bio-molecules; linking the methodologies developed in this research to applications in industry; and developing an international (China and Brazil) collaborative research and education program on bio-molecular recognition.

分子识别是现代分子生物学的核心问题之一。 虽然刚性和半刚性结合已经被广泛探索，但在细胞的过程和功能中经常发现的具有大构象变化的柔性结合还没有被很好地理解。 该项目的目标是由分子和细胞生物科学部的分子生物物理学和化学部的理论和计算化学计划共同支持，建立一个理论框架来理解基本机制（灵活性如何帮助识别）并量化灵活结合的动力学路径。柔性结合的研究将分三个步骤进行：首先，建立柔性结合的理论框架，以了解柔性对热力学性质的作用。 其次，路径积分形式主义将被开发来量化的动力学绑定路径，了解柔性和折叠的柔性绑定的动力学的作用，并回答问题的绑定的基本机制，如设置的动力学路径的绑定将更有可能采取。第三，将探讨灵活性如何帮助原子级识别的问题。这项研究的主要智力价值是通过发展一个新的理论框架和识别动力学路径来理解灵活的生物分子识别的基本机制。所获得的原理可用于指导特异性识别复合物的原子水平动力学路径模拟，克服传统的计算瓶颈，探索动力学函数。该项目的教育方面将对来自世界各地的学生在生物/化学/物理的界面上进行跨学科研究产生广泛的影响，首先是美国的学生。美国，中国和巴西。将把研究和教育工作结合起来。这包括为本科生和研究生设计生物分子识别和计算生物学的跨学科课程和课程;撰写一本关于生物分子能源景观的书;将本研究中开发的方法与工业应用联系起来;以及开发国际（中国和巴西）合作研究和教育计划生物分子识别。