PIP2对TRP通道功能的调控起到了至关重要的作用。然而，其微观分子机理至今仍不清晰。得益于TRP通道高分辨率冷冻电镜结构的解析（3.4Å），使我们可以从微观水平对其调控机理进行研究。但是，静态的结构信息难以建立起TRP通道动态结构与功能之间的联系，计算生物学的应用弥补了实验在时空尺度和动态学研究上的不足。本项目中，针对TRP通道冷冻电镜结构分辨率粗、尺度大的特点，我们拟建立多尺度的分子动力学模拟方案，并通过高精度可极化力场研究PIP2对TRP通道调控的微观分子机理，为理解TRP通道的活化机理提供强有力的理论支撑和并为以TRP通道为靶点的药物研发提供高效的研究工具。

Membrane phosphatidylinositol-4,5-bisphosphate (PIP2) is critical for regulating the function of transient receptor potential (TRP) ion channels. However, the molecular mechanism of this process is still unknown. The available of the structural information of TRP channels determined by electron cryo-microscopy provide us the opportunity to study the underling mechanism at a microscopic level, but the static structure of TRP channels could not bring us much insight into the relationship between its function and dynamic motions. Computational biology has become a powerful tool to compensate for the experimental limitation by bridging the protein dynamics and its function. In the proposal, we intend to establish the multi-scale molecular dynamic simulation protocol to investigate the dynamic behaviors of TRP channel regulated by PIP2. The next generation polarizable force field could also be utilized to accurately study the molecular mechanism at atomic level. Thus, our investigation would build a strong theoretical basis in understanding the mechanism of TRP channel activation and offer a highly efficient methodology for TRP targeted drug discovery.