Department of Theoretical and Computational Biophysics, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
Biophys J. 2011 Aug 17;101(4):809-17. doi: 10.1016/j.bpj.2011.06.010.
Presently, most simulations of ion channel function rely upon nonatomistic Brownian dynamics calculations, indirect interpretation of energy maps, or application of external electric fields. We present a computational method to directly simulate ion flux through membrane channels based on biologically realistic electrochemical gradients. In close analogy to single-channel electrophysiology, physiologically and experimentally relevant timescales are achieved. We apply our method to the bacterial channel PorB from pathogenic Neisseria meningitidis, which, during Neisserial infection, inserts into the mitochondrial membrane of target cells and elicits apoptosis by dissipating the membrane potential. We show that our method accurately predicts ion conductance and selectivity and elucidates ion conduction mechanisms in great detail. Handles for overcoming channel-related antibiotic resistance are identified.
目前，大多数离子通道功能模拟都依赖于非原子布朗动力学计算、能量图谱的间接解释或外加电场的应用。我们提出了一种基于生物现实电化学梯度直接模拟离子通过膜通道的计算方法。与单通道电生理学非常相似，实现了与生理和实验相关的时间尺度。我们将我们的方法应用于来自致病性脑膜炎奈瑟菌的细菌通道 PorB，在奈瑟菌感染过程中，该通道插入靶细胞的线粒体膜，并通过耗散膜电位引发细胞凋亡。我们表明，我们的方法可以准确预测离子电导率和选择性，并详细阐明离子传导机制。确定了克服与通道相关的抗生素耐药性的方法。
