报告题目：Atomistic mechanism for the activation and desensitization of an AMPA-subtype glutamate receptor
报告人：董昊 博士
报告地点：江苏省生物材料与器件重点实验室（小兰搂） 三楼会议室
报告时间：2013年5月31日 上午10:00
摘要：
Ionotropic glutamate receptors (iGluRs) mediate fast excitatory synaptic transmission in the central nervous system. Upon agonist binding, an iGluR opens to allow the flow of cations and subsequently enters into a desensitized state. It remains unclear how agonist binding to the ligand-binding domain (LBD) is transmitted to the transmembrane domain (TMD) for channel activation and desensitization. Here we report molecular dynamics simulations of an AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid)-subtype iGluR in explicit water and membrane. Channel opening and closing were observed in simulations of the activation and desensitization processes, respectively. The motions of the LBD–TMD linkers along the central axis of the receptor and in the lateral plane contributed cooperatively to channel opening and closing. The detailed mechanism of channel activation and desensitization suggested by the simulations here is consistent with existing data and may serve as a guide for new experiments and for the design of pharmacological.
董昊博士主要从事生物物理和计算化学方面的研究，研究成果发表在Science, PNAS, Nature Communications, PLoS Computational Biology, Biochemistry等国际学术期刊上，08年博士毕业于南京大学物理化学专业（师从黎书华教授）。09年至11年在佛罗里达州立大学（Florida State University）进行博士后研究（师从Huan-Xiang Zhou教授）。12年至今在天普大学（Temple University）从事博士后研究（师从Michael L. Klein院士）。现在的课题主要是采用计算模拟的方式研究膜蛋白的结构、机制等问题。研究的体系包括 M2 proton channel (Science 2010, Chem Sci 2013), glutamate receptor (Nat Commu 2011), P2X4 receptor (PNAS 2012)等。 附件是董昊博士的详细介绍。
