柔性生物分子结合识别的自组装理论与模拟

The goal of Molecular biology is to understand the biological function. Molecular recognition is a very important self-assembly process in Chemistry and Biology. Recognition is also important between the drug molecules and biological receptor target molecular. And it has important guiding significance to understand the molecular recognition for design new drugs. Molecular flexibility dynamics plays an important role in the determination of biological structure and function as well as quantitative description. The long-term goal of molecular biology is to understand the flexible biomolecular recognition. The project aims to build a flexible ( folding ) recognition kinetics theory, explore how flexible self-assembly process realize the function of molecular recognition, and then improve the drug design. This project will fill the blank on studying molecule flexible self-assembled recognition, reveals flexible recognition essence in the macroscopical thermodynamics ( stability ) and micro level quantification through the development of the energy landscape theory framework, develop path integral theory frame, determine the non-equilibrium dynamic behavior of the self assembly molecular recognition, and validate the molecular recognition path associated with the experimental group cooperation. The traditional self-assembly concept that structure determines the function will be changed to that structure and flexible ( folding ) both determine the function. We will develop the rigid docking and induced fit method to describe flexible ( folding ) conformational transitions in self-assembly process of molecular recognition. This project is a cross discipline of Mathematics, Physics, Chemistry and Biology.

分子生物学的目标是了解生物功能。分子识别是化学和生命中极重要的自组装过程，也是药物分子与生物受体靶分子相互识别的关键所在，了解分子识别对设计新型药物具有重要的指导意义。分子的柔性动力学在确定生物结构和功能以及对其量化描述起着重要作用。分子生物学的长远目标是要了解柔性的生物分子识别。本项目目标是建立一个柔性（折叠）识别动力学的理论框架，发现柔性自组装怎样实现分子识别功能，进而改善药物设计。本项目将填补研究分子柔性自组装识别的空白，通过发展能量地貌理论框架，在宏观热力学（稳定性）和微观水平上量化揭示柔性识别本质；发展路径积分的理论框架，确定分子识别自组装非平衡动力学行为，并与相关实验小组合作，验证分子识别路径。结构决定功能的传统自组装观念将改变成为结构与柔性（折叠）一起决定功能。我们将把刚性对接及诱导契合方法发展成可描述柔性（折叠）构象转变的大分子识别自组装过程。本项目是数理化生学科的交叉。

分子生物学的目标是了解生物功能。分子识别是化学和生命中极重要的自组装过程，也是药物分子与生物受体靶分子相互识别的关键所在，了解分子识别对设计新型药物具有重要的指导意义。分子的柔性动力学在确定生物结构和功能以及对其量化描述起着重要作用。分子生物学的长远目标是要了解柔性的生物分子识别。本项目建立了一个柔性（折叠）识别动力学的理论框架，发现柔性自组装怎样实现分子识别功能，进而改善药物设计。本项目填补了研究分子柔性自组装识别的空白，通过发展能量地貌理论框架，在宏观热力学（稳定性）和微观水平上量化揭示柔性识别本质；发展路径积分的理论框架，确定分子识别自组装非平衡动力学行为，并与相关实验小组合作，验证了分子识别路径。结构决定功能的传统自组装观念改变成为结构与柔性（折叠）一起决定功能。我们把刚性对接及诱导契合方法发展成可描述柔性（折叠）构象转变的大分子识别自组装过程。本项目是数理化生学科的交叉。