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

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.

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。

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。因缺乏表征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。我们发展了飞秒时间分辨和频光谱与太赫兹光谱结合的测量平台。太赫兹光谱测量范围为0.1-3THz，通过400nm或800nm的激发，可以实现飞秒时间分辨的太赫兹光谱测量，太赫兹瞬态光谱检测灵敏度ΔT/T为1/10000，实现了从晶格振动到化学键振动的测量。揭示了界面蛋白质与水分子间的耦合作用及其共振能量传递捷径；揭示了pH值、磷脂双层膜组分对界面蛋白质结构转变动力学的影响规律以及界面蛋白质结合水驱动淀粉样蛋白Aβ42错误折叠动力学机制；揭示了界面蛋白质结合水影响界面蛋白质非谐性、能量转移效率规律以及界面水影响界面摩擦系数的规律；证实了常温常压下聚四氟乙烯表面存在“疏水的水层”，疏水的水层存在可很好解释聚四氟乙烯具有抗冻、抗污等特异性质。各项工作按计划顺利并完满完成，目前已在Nat. Commun., JACS, Angew. Chem. Int. Ed., J. Phys. Chem. Lett., Chem. Comm.等学术期刊上发表研究论文18篇，全部标注课题号。项目负责人被邀请在国内外多个专业学术会议上作邀请报告13次，2019年获国家杰出青年科学基金资助，培养博士2名、硕士1名，博士后出站1名并成为中科大特任副研究员，完满实现项目的既定目标和任务。发展的测量平台将在生物、电化学、能源等复杂体系界面研究中展现出巨大的潜力。