COMPUTER MODELING OF THE ANTIAMOEBIN ION CHANNEL

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。 分子动力学模拟是为了确定跨膜多肽通道的潜在多聚体形式中的哪一种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方程获得的电导的估计值得到了一致的结果，表明离子在通道内的运动可以令人满意地描述为扩散。计算的八聚体通道的电导明显高于单通道记录中测得的电导，而四聚体似乎不导电。在150 mV和75 mV时，该六聚体的电导分别为115+/-34pS和74+/-20pS，与在75 mV下测得的90pS令人满意地一致。在此基础上，我们提出抗阿米巴通道由6个单体组成。它的孔足够大，可以容纳K+和Cl-离子，而它们的第一个溶剂化外壳完好无损。K+遇到的自由能垒仅为2.2kcal/mol，而Cl-遇到的自由能垒高得多，接近5kcal/mol。这种差异使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。

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.