复杂物理因素调控的蛋白质功能结构形成、运动和相互作用

Protein molecules are a kind of typical soft condensed-matter systems. They undergo various structural changes for the formation of functional structure units and the execution of biological functions, including folding, aggregations, allosteric motions, and so on. These dynamic processes are under the cooperative and subtle regulations of various physical factors, such as metal ions, external forces, and complex interfaces and so on. The physical factors bring tremendous complexities to the structural changes of protein molecules, making such systems a fascinating research topic with rich physical contents. How do these physical factors interact with protein molecules? What are physical mechanisms that underlie the regulations of the structural formation and functional dynamics of proteins? The researches on these questions are the frontiers of the interdisciplinary studies between physics and biology. In our project, we will concentrate on several representative protein systems, and study the effects of several physical factors (including metal ions, external forces, and/or nano-scaled particles as well as complex interfaces) on the dynamics of structural formations and functional motions of proteins. Both experimental and simulation methods will be employed in our project, including the common molecular-biology techniques, single-molecular force spectroscopy, and various models and methods for large-scale molecular simulations. Through detailed characterizations on the dynamics of proteins and comprehensive analysis on the related physical mechanisms, we expect to establish a quantitative theory on how the concerned physical factors regulate the dynamics of proteins. These studies could deepen the understanding on the physical properties of biological macromolecules, realize the quantitative descriptions of related processes, and further bring some fundamental insights to the design of protein-based functional materials.

蛋白质分子是典型的软物质体系，其折叠、聚集、变构等功能结构形成和构象运动过程是生命系统的结构组织和功能执行中的关键环节。这些动力学过程受到金属离子、生物外力和复杂界面等物理因素的协同作用和调控，蕴含着丰富的物理内涵。这些物理因素是如何与蛋白质分子相互作用？通过怎样的物理机制调控蛋白质分子功能结构形成和构象运动？这些问题的研究是当前物理学与生物学交叉的前沿。本项目针对几个典型蛋白质体系，综合运用分子生物学实验技术、单分子实验手段和大规模模拟计算方法，围绕蛋白质功能结构形成和构象运动过程，系统研究金属离子、生物外力和纳米粒子与固体表面等多种物理因素的作用和影响，刻画相关动力学过程，分析和揭示其物理机制，建立相关物理因素调控下的蛋白质动力学的定量理论。从而深化对生物分子体系物理特性的认识，实现相关过程的定量刻画，并且对有关功能材料设计提供基础性参考。

细胞环境下，蛋白质等生物大分子受到机械力、辅因子等复杂物理和化学因素的调控。因此，研究复杂物理化学因素调控下的生物大分子结构和功能动力学对理解细胞环境下的生物过程至关重要。本项目围绕复杂物理因素调控的蛋白质功能结构形成、运动和相互作用等方面，按照预定设想，理论结合实验，很好地完成了研究任务，并做了重要拓展。在金属离子、二硫键、机械力、二维界面、磷酸化翻译后修饰等复杂物理化学因素调控下的蛋白质、核酸结构形成和基本物理特性及其复杂相互作用，多肽分子和无序结构特性、生物分子材料结构和物理特性、以及生物大分子多尺度理论等方面取得了多个重要研究成果。已在相关期刊上发表论文30余篇，部分成果发表在Phys.Rev.Lett(1篇)，PNAS(2篇)，Nature Comm.(2篇)，JACS(1篇)和Angew.Chem.(1篇)等重要期刊上，并应邀在结构生物学重要综述期刊Curr. Opin. Struct. Biol.(2015)和物理学综述期刊Adv. Phys.-X (2016)撰写综述论文。本项目研究成果对理解细胞环境下的生物大分子的折叠组装、功能运动、以及基于生物大分子的材料设计具有重要的科学意义。

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