COMPUTER MODELING OF THE ANTIAMOEBIN ION CHANNEL

抗阿米巴离子通道的计算机建模

• 批准号: 8363639
• 负责人: ANDREW POHORILLE
• 金额: $ 1.01万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8363639
• 关键词: Agreement; Cations; Computer Simulation; Equation; Event; Free Energy; Funding; Grant; Imagery; Informatics; Ion Channel; Ions; Measures; Motion; National Center for Research Resources; Principal Investigator; Research; Research Infrastructure; Resources; Source; United States National Institutes of Health; antiamoebin; base; biocomputing; cost; molecular dynamics; monomer; statistics

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. Molecular dynamics simulations were carried out in order to ascertain which of the potential multimeric forms of the transmembrane peptaibol channel, antiamoebin, is consistant with its measured conductance. Estimates of the conductance obtained through counting ions that cross the channel and by solving the Nernst-Planck equation yield consistent results, indicating that the motion of ions inside the channel can be satisfactorily described as diffusive. The calculated conductance of octameric channels is markedly higher than the conductance measured in single channel recordings, whereas the tetramer appears to be non-conducting. The conductance of the hexamer was estimated to be 115+/-34 pS and 74+/-20 pS, at 150 mV and 75 mV, respectively, in satisfactory agreement with the value of 90 pS measured at 75 mV. On this basis we propose that the antiamoebin channel consists of six monomers. Its pore is large enough to accommodate K+ and Cl- ions with their first solvation shells intact. The free energy barrier encountered by K+ is only 2.2 kcal/mol whereas Cl- encounters a substantially higher barrier of nearly 5 kcal/mol. This difference makes the channel selective for cations. Ion crossing events are shown to be uncorrelated and follow Poisson statistics.

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。 进行了分子动力学模拟，以确定跨膜 peptaibol 通道（抗阿米巴）的哪种潜在多聚体形式与其测量的电导一致。 通过计算穿过通道的离子和求解 Nernst-Planck 方程获得的电导估计值得到一致的结果，表明通道内离子的运动可以令人满意地描述为扩散的。八聚体通道的计算电导明显高于单通道记录中测量的电导，而四聚体似乎不导电。六聚体的电导在 150 mV 和 75 mV 下估计分别为 115+/-34 pS 和 74+/-20 pS，与在 75 mV 下测量的 90 pS 值令人满意地一致。在此基础上，我们提出抗阿米巴通道由六个单体组成。它的孔隙足够大，可以容纳 K+ 和 Cl- 离子，并且它们的第一个溶剂化壳完好无损。 K+ 遇到的自由能垒仅为 2.2 kcal/mol，而 Cl- 遇到的自由能垒要高得多，接近 5 kcal/mol。这种差异使得通道对阳离子具有选择性。离子交叉事件被证明是不相关的并且遵循泊松统计。