Amphotericin B, an antifungal drug with a long history of use, forms fungicidal ion-permeable channels across cell membranes. Using solid-state nuclear magnetic resonance spectroscopy and molecular dynamics simulations, we experimentally elucidated the three-dimensional structure of the molecular assemblies formed by this drug in membranes in the presence of the fungal sterol ergosterol. A stable assembly consisting of seven drug molecules was observed to form an ion conductive channel. The structure is somewhat similar to the upper half of the barrel-stave model proposed in the 1970s but substantially different in the number of molecules and in their arrangement. The present structure explains many previous findings, including structure-activity relationships of the drug, which will be useful for improving drug efficacy and reducing adverse effects.

中文翻译：

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两性霉素 B 组装成七分子离子通道：核磁共振和分子动力学研究

两性霉素 B 是一种具有悠久使用历史的抗真菌药物，可在细胞膜上形成杀真菌离子可渗透通道。使用固态核磁共振光谱和分子动力学模拟，我们通过实验阐明了这种药物在真菌甾醇麦角甾醇存在下在膜中形成的分子组装体的三维结构。观察到由七个药物分子组成的稳定组装形成离子传导通道。该结构有点类似于 1970 年代提出的桶形板条模型的上半部分，但分子数量和排列方式却大不相同。目前的结构解释了许多以前的发现，包括药物的构效关系，