Schwöbel Johannes A H, Ebert Andrea, Bittermann Kai, Huniar Uwe, Goss Kai-Uwe, Klamt Andreas
BIOVIA, Dassault Systèmes Deutschland GmbH, Imbacher Weg 46, D-51379 Leverkusen, Germany.
UFZ-Helmholtz Centre for Environmental Research, Permoserstraße 15, D-04318 Leipzig, Germany.
J Phys Chem B. 2020 Apr 23;124(16):3343-3354. doi: 10.1021/acs.jpcb.9b11728. Epub 2020 Apr 13.
We present a new and entirely mechanistic COSMO method to predict passive membrane permeabilities for neutral compounds, as well as anions and cations. The COSMO approach is based on compound-specific free energy profiles within a membrane of interest from COSMO-RS (conductor-like screening model for realistic solvation) calculations. These are combined with membrane layer-specific diffusion coefficients, for example, in the water phase, the polar head groups, and the alkyl tails of biochemical phospholipid bilayers. COSMO-RS utilizes first-principle quantum chemical structures and physically sound intermolecular interactions (electrostatic, hydrogen bond, and van der Waals). For this reason, it is unbiased toward different application scenarios, such as in cosmetics and industrial chemical or pharmaceutical industries. A fully predictive calculation of passive permeation through phospholipid bilayer membranes results in a performance of = 0.92; rmsd = 0.90 log units for neutral compounds and anions, as compared to gold standard black lipid membrane experiments. It will be demonstrated that new membrane types can be generated by the related COSMO method and directly used for permeability studies by COSMO.
我们提出了一种全新的、完全基于机理的COSMO方法，用于预测中性化合物以及阴离子和阳离子的被动膜渗透性。COSMO方法基于通过COSMO-RS（真实溶剂化的导体类筛选模型）计算得出的在感兴趣膜内的化合物特定自由能分布。这些自由能分布与膜层特定的扩散系数相结合，例如在水相、生化磷脂双层的极性头部基团和烷基尾部中的扩散系数。COSMO-RS利用第一性原理量子化学结构和合理的分子间相互作用（静电、氢键和范德华力）。因此，它对不同的应用场景没有偏向性，如在化妆品、工业化学品或制药行业。与金标准黑脂质膜实验相比，通过磷脂双层膜的被动渗透的完全预测性计算得出，对于中性化合物和阴离子，相关系数为0.92；均方根偏差为0.90对数单位。将证明，相关的COSMO方法可以生成新的膜类型，并直接用于COSMO的渗透性研究。
