界面生物大分子与其结合水耦合动力学的飞秒时间分辨非线性光谱研究

阐明生物分子与其结合水之间的耦合关系是揭示生物水如何影响生物功能以及获得蛋白质抗冻机理深层次理解的核心。因缺乏区分生物分子及其结合水两者超快动力学行为的有效技术，目前对该耦合作用了解甚少。本项目拟发展和完善飞秒时间分辨和频光谱与太赫兹光谱技术，以多肽、抗冻蛋白等生物分子与水溶液之间形成的界面为研究对象，系统研究生物分子与其结合水耦合作用这一重要前沿科学问题。在飞秒时间尺度上精确测量生物分子及其结合水在不同条件下的分子结构与超快动力学行为，并将界面蛋白质二级结构与侧链、界面水、反映蛋白质和结合水涨落的低频集体运动等三者的超快动力学关联起来，在分子水平上诠释生物分子与其结合水在动力学上的耦合本质以及蛋白质抗冻机理。项目的成功将有助于我们深入认识结合水影响生物结构和功能的本质和规律，进而揭示生物分子生理功能背后的物理化学机制，最终为控制与神经退化型疾病相关的早期蛋白质错误折叠等过程提供新思路。

Elucidating the ultimate coupling relationship between biomolecules and the water molecules in their vicinity is the key for revealing how the biological water affects the biological function and getting an in-depth insight into the mechanism of antifreeze proteins. However, the ultimate coupling interaction between them remains substantially unexplored because of lack of effective tools to separate the ultrafast dynamics of biomolecules and their associated water. In this project, a femtosecond time-resolved sum-frequency generation vibrational spectroscopy and Terahertz spectroscopy will be developed. We will apply this time-resolved system to resolve the frontier scientific issue on the coupling dynamics between biomolecules and their associated water molecules by systematically investigating the ultrafast dynamics occurring at the interface between peptides(antifreeze proteins) and water solution. Namely, we will accurately characterize the molecular structure and ultrafast dynamics of the biomolecules and their associated water at different conditions at the femtosecond time scale. On this basis, we will correlate the ultrafast dynamics of protein secondary structures and their sidechains, interfacial water, low-frequency collective motions that response the fluctuation of proteins and their associated water. This correlation may help to reveal the nature of dynamic coupling interaction between biomolecules and their associated water, as well as the mechanism of antifreeze proteins at the molecular level. The success of the project will provide us with a molecular-level understanding on how the biological water influences the biomolecule structures and functions, and thus reveal the nature of the biological functions in physical chemistry. The results from this project will provide important clues to control the biological processes such as the initial protein misfolding associated with the neurodegenerative diseases.