Coordination Funds

dfg研究单元2518“离子通道和转运体的功能动力学- DynIon”结合实验和计算策略来研究离子通道和转运体的功能。在第一个资助期工作的基础上，DynIon将在第二个资助期重点研究这些蛋白质的关键功能过程，如离子渗透、配体/底物结合和易位，以及电压或配体依赖性的功能修饰。DynIon将专注于四种蛋白质类别：(1)K+通道（例如K2P通道，电压门控K+通道，病毒K+通道），(2)环核苷酸调节通道（CNG和HCN通道），(3)谷氨酸受体，(4)谷氨酸转运蛋白（SCL1, SCL17）。我们将采用各种最先进的实验方法，从异种表达，膜片钳记录，荧光法到纯化蛋白质的光谱学，人工膜或纳米片的重构以及冷冻电子显微镜。这些技术将与计算技术相结合，如全原子MD模拟、QM/MM模拟、自由能计算、计算电生理学、刚性分析、马尔可夫状态建模、各向异性网络建模、卡尔曼滤波、玻尔兹曼发生器和深度学习。DynIon将继续在实验室实验和先进的计算机分析之间发展协同作用，以研究原子分辨率的离子通道和转运体。

The DFG-Research Unit 2518 ‘Functional dynamics of ion channels and transporters - DynIon’ combines experimental and computational strategies to study the function of ion channels and transporters. Based on the work of the first funding period, DynIon will focus in the second funding period on key functional processes of these proteins, such as ion permeation, ligand/substrate binding and translocation as well as voltage- or ligand-dependent modification of function. DynIon will focus on four protein classes: (1) K+ channels (e.g. K2P channels, voltage-gated K+ channels, viral K+ channels), (2) cyclic-nucleotide regulated channels (CNG and HCN channels), (3) glutamate receptors, and (4) glutamate transporters (SCL1, SCL17). We will employ a variety of state-of-the-art experimental approaches, ranging from heterologous expression, patch-clamp recording, fluorometry to spectroscopy on purified proteins, reconstitution in artificial membranes or nanodiscs and cryo-electron microscopy. These techniques will be combined with computational techniques such as all-atom MD simulations, QM/MM simulations, free energy calculations, computational electrophysiology, rigidity analyses, Markov-state modeling, anisotropic network modeling, Kalman filtering, Boltzmann generators, and deep learning. DynIon will continue to develop a synergy between laboratory experiments and advanced computer analyses to study ion channels and transporters at atomic resolution.