ALL ATOM MOLECULAR DYNAMICS SIMULATION OF CONNEXIN HEMICHANNEL VOLTAGE GATING

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 对嵌入在显式POPC膜和溶剂系统中的43E1半通道进行10.5°S全原子模拟所需的时间较大，以探索通道在从开放状态转变为闭合状态时随电压变化的构象路径。我们模拟的基本策略是以1？S的增量增加施加的电势和/或系统温度，同时监控电压相关(电荷相互作用)和电压无关(疏水相互作用)属性的轨迹，这些属性与开放通道的稳定性直接相关，并且必须随着通道关闭而改变。通过实验确定了孔道在开启和关闭状态下的构象，并提供了一种验证模拟终点的方法。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Time is requested to perform a 10.5 ¿s all atom simulation of the 43E1 hemichannel embedded in an explicit POPC membrane and solvent system with a large applied electric field to explore the conformational path made by the channel as it transits from the open to closed state in response to voltage. The basic strategy of our simulation is to increase the applied potential and/or system temperature in 1 ¿s increments while monitoring the trajectories of voltage-dependent (charge interactions) and voltage-independent (hydrophobic interactions) properties that are directly related to stability of the open channel and must change with channel closure. The conformations of the channel pore in the open and closed states have been determined experimentally and provide a means of validating the end point of the simulation.