离子通道与转运蛋白结构生物学 · 基于结构的药物设计Structural Biology of Ion Channels & Transporters · Structure-Based Drug Design
以 X 射线晶体学与单颗粒冷冻电镜为核心技术，结合蛋白质从头设计与药物筛选，在 One Health 理念下研究离子通道、受体及转运蛋白的结构与功能。 Anchored by X-ray crystallography and single-particle cryo-EM, and integrated with de novo protein design and drug screening, we study the structure and function of ion channels, receptors, and transporters under the One Health framework.
利用同步辐射光源对膜蛋白及其配体复合物进行高分辨率晶体结构解析，在原子分辨率水平揭示底物识别、离子选择性及药物结合的结构基础与分子机制。 Using synchrotron radiation to determine atomic-resolution crystal structures of membrane proteins and their ligand complexes, revealing the molecular basis of substrate recognition, ion selectivity, and drug binding.
突破膜蛋白结晶瓶颈，在近生理条件下捕获离子通道与 ABC 转运蛋白在静息态、预转运态及催化中间态的高分辨率结构，揭示其动态转运机制。 By overcoming the crystallization bottleneck inherent to membrane proteins, we capture multiple conformational states under near-physiological conditions, revealing the dynamic transport mechanisms of ion channels and ABC transporters.
基于结构信息与计算设计方法，从头设计具有特定功能的蛋白质分子，开发新型膜蛋白工具与探针，为靶向干预和功能研究提供新型分子平台。 Leveraging structural information and computational design principles to engineer proteins with defined functions de novo, developing novel membrane protein tools and probes for targeted intervention and functional studies.
以解析的高分辨率结构为基础，开展基于结构的虚拟筛选与高通量实验筛选，鉴定靶向离子通道和转运蛋白的先导化合物，推动抗寄生虫与抗菌新药开发。 Building on high-resolution structures, we conduct structure-based virtual screening and high-throughput experimental screening to identify lead compounds targeting ion channels and transporters, thereby advancing antiparasitic and antimicrobial drug discovery.
离子通道和转运蛋白在多种人类疾病中发挥关键作用。我们利用冷冻电镜和X射线晶体学等技术解析疾病相关离子通道和转运蛋白的高分辨率结构，阐明其门控、底物识别与转运的分子机制，并基于结构开展药物设计与筛选。 Ion channels and transporters play critical roles in human diseases. We employ cryo-EM and X-ray crystallography to determine high-resolution structures, elucidate molecular mechanisms of gating and transport, and conduct structure-based drug design and screening.
以线虫关键靶点为结构模型，阐明驱虫药物的作用机制，鉴定新型药物靶点，并开展高通量药物筛选，为线虫病的防治和公共卫生安全提供新策略。 Using key nematode targets as structural models, we elucidate anthelmintic mechanisms, identify novel drug targets, and perform high-throughput screening to provide new strategies for nematode control and public health.