ALL ATOM MOLECULAR DYNAMICS SIMULATION OF CONNEXIN HEMICHANNEL VOLTAGE GATING

连接蛋白半通道电压门控的全原子分子动力学模拟

• 批准号: 8364232
• 负责人: Thaddeus Andrew Bargiello
• 金额: $ 0.11万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-15 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8364232
• 关键词: Biomedical Research; Charge; Connexins; Funding; Grant; High Performance Computing; Hydrophobic Interactions; Membrane; Molecular Conformation; Monitor; National Center for Research Resources; Principal Investigator; Property; Research; Research Infrastructure; Resources; Solvents; Source; System; Temperature; Time; United States National Institutes of Health; cost; electric field; molecular dynamics; response; simulation; voltage

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.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 需要时间对嵌入显式 POPC 膜和溶剂系统中的 43E1 半通道进行 10.5 s 全原子模拟，并施加大电场，以探索通道响应电压从打开状态转变为关闭状态时形成的构象路径。我们模拟的基本策略是以 1 µs 的增量增加施加的电势和/或系统温度，同时监测电压相关（电荷相互作用）和电压无关（疏水相互作用）特性的轨迹，这些特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。通道孔在打开和关闭状态下的构象已通过实验确定，并提供了验证模拟终点的方法。