Small, hydrophilic molecules, including most important antibiotics in clinical use, cross the Gram-negative outer membrane through the water-filled channels provided by porins. We have determined the X-ray crystal structures of the principal general porins from three species of Enterobacteriaceae, namely Enterobacter aerogenes, Enterobacter cloacae, and Klebsiella pneumoniae, and determined their antibiotic permeabilities as well as those of the orthologues from Escherichia coli. Starting from the structure of the porins and molecules, we propose a physical mechanism underlying transport and condense it in a computationally efficient scoring function. The scoring function shows good agreement with in vitro penetration data and will enable the screening of virtual databases to identify molecules with optimal permeability through porins and help to guide the optimization of antibiotics with poor permeation.

中文翻译：

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将药物带入革兰氏阴性细菌：通过一般孔蛋白渗透的合理规则

亲水性小分子（包括临床上最重要的抗生素）通过孔蛋白提供的充满水的通道穿过革兰氏阴性外膜。我们已经确定了三种肠杆菌科细菌的主要普通孔蛋白的X射线晶体结构，即产气肠杆菌，阴沟肠杆菌和肺炎克雷伯菌，并确定了它们的抗生素通透性以及大肠杆菌的直向同源物的通透性。。从孔蛋白和分子的结构出发，我们提出了一种潜在的运输物理机制，并将其浓缩为计算有效的评分功能。评分功能与体外渗透数据显示出良好的一致性，并将能够筛选虚拟数据库，以鉴定通过孔蛋白具有最佳渗透性的分子，并有助于指导渗透性较差的抗生素的优化。