学术报告

报告题目：Simulation and Modeling of Ion Channel Functional Mechanisms and Transport

报 告 人：Huan-Xiang Zhou 教授

时    间：2013年6月4日  下午2:00

地    点：炳麟图书馆720会议室    

                                                            苏州大学医学部欧洲杯官网

                                  苏州大学放射医学及交叉学科研究院

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Huan-Xiang Zhou 教授简介

1984年毕业于武汉大学空间物理系，1988年获Drexel University博士，1990-1995年在美国NIH做博士后，1995-1998年任香港大学生物化学系助理副教授，1998-2002年任德雷塞尔大学副教授，2002年起任美国佛罗里达州立大学（Florida State University）副教授及教授。曾获得CUSPEA Graduate Fellowship, Drexel University；Elected Fellow of the American Association for the Advancement of Science；Elected Fellow of the American Physical Society；Distinguished Research Professor等多项荣誉。主要研究领域：Quantitative understanding of biological processes in the cellular context, based on fundamental physical principles. (1) Kinetics of protein association; (2) Functional mechanisms of ion channels; (3) Crowding and confinement effects in cellular environments。目前以PI身份获得包括NIH的R01在内多项项目资助。近年以通讯作者发表的代表性论文发表在Science，Proc. Natl. Acad. Sci.，J. Am. Chem. Soc.等杂志上。

报告摘要：

Ion channels play vital cellular functions and are important drug targets. How an external stimulus (e.g., change in pH or cross-membrane voltage, or binding of a ligand) triggers the opening of an ion channel is at the core of its functional mechanism. We have used molecular dynamics simulations and other computational techniques to develop models for the functional mechanisms of pH-gated and ligand-gated channels [1-3]. A very useful way to validate these mechanistic models is to compare changes in residue solvent accessible areas against substituted cysteine accessibility measurements [4]. For the M2 proton channel of the influenza virus, based on the proposed functional mechanism [1], we have developed a theory for calculating the rate of ion transport. The permeant proton is modeled as binding obligatorily to a histidine tetrad within the channel pore and then being released to the other side of the membrane. The theory quantitatively rationalizes experimental I-V relations [5] and solvent isotope effect [6]. Lately, we have been investigating possible perturbations of membrane protein structures by membrane mimetics, and developing ways to recognize such perturbations and computational methods to correct them [7].

1. M. Sharma, M. Yi, H. Dong, H. Qin, E. Peterson, D. D. Busath, H.-X. Zhou, and T. A. Cross (2010). Insight into the mechanism of the influenza A proton channel from a structure in a lipid bilayer. Science 330, 509-512.

2. H. Dong and H.-X. Zhou (2011). Atomistic mechanism for the activation and desensitization of an AMPA-subtype glutamate receptor. Nat. Commun. 2, 354.

3. J. Du, H. Dong, and H.-X. Zhou (2012). Gating mechanism of a P2X4 receptor developed from normal mode analysis and molecular dynamics simulations. Proc. Natl. Acad. Sci. USA. 109, 4140-4145.

4. M. Yi, H. Tjong, and H.-X. Zhou (2008). Spontaneous conformational change and toxin binding in α7 nicotinic acetylcholine receptor: insight into channel activation and inhibition. Proc. Natl. Acad. Sci. 105, 8280-8285.

5. H.-X. Zhou (2011). A theory for the proton transport of the influenza virus M2 protein: extensive test against conductance data. Biophys. J. 100, 912-921.

6. H.-X. Zhou (2011). Mechanistic insight into the H2O/D2O isotope effect in the proton transport of the influenza virus M2 protein. J. Membr. Biol. 244:93-96.

7. H.-X. Zhou and T. A. Cross (2013). Influences of membrane mimetic environments on membrane protein structures. Annu. Rev. Biophys. 42:361-392.