The Journal of Membrane Biology ( IF 2.3 ) Pub Date : 2021-02-10 , DOI: 10.1007/s00232-021-00170-5 Victor Vasquez-Montes 1 , Alexey S Ladokhin 1
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Abstract
Hydropathy plots are a crucial tool to guide experimental design, as they generate predictions of protein–membrane interactions and their bilayer topology. The predictions are based on experimentally determined hydrophobicity scales, which provide an estimate for the propensity and stability of these interactions. A significant improvement to the accuracy of hydropathy analyses was provided by the development of the popular Wimley–White interfacial and octanol hydrophobicity scales. These scales have been previously incorporated into the freely available MPEx (Membrane Protein Explorer) online application. Here, we introduce a substantial update to MPEx that allows for the consideration of electrostatic contributions to the bilayer partitioning free energy. This component originates from the Coulombic attraction or repulsion of charges between proteins and membranes. Its inclusion in hydropathy calculations increases the accuracy of hydropathy plot predictions and extends their use to more complex systems (i.e., anionic membranes). We illustrate the application of this analysis to studies on the membrane selectivity of antimicrobial peptides, the membrane partitioning of ion-channel gating modifiers, and the amyloid proteins α-synuclein and Tau, as well as pH-dependent bilayer interactions of diphtheria toxin and apoptotic inhibitor Bcl-xL.
Graphic Abstract
中文翻译：
扩展 MPEx 亲水性分析以解释静电对蛋白质与阴离子膜相互作用的贡献
摘要
亲水图是指导实验设计的重要工具，因为它们可以预测蛋白质-膜相互作用及其双层拓扑结构。这些预测是基于实验确定的疏水性尺度，它提供了对这些相互作用的倾向和稳定性的估计。流行的 Wimley-White 界面和辛醇疏水性标度的开发显着提高了亲水分析的准确性。这些量表之前已被纳入免费提供的 MPEx（膜蛋白资源管理器）在线应用程序中。在这里，我们对 MPEx 进行了重大更新，允许考虑静电对双层分配自由能的贡献。该成分源于蛋白质和膜之间电荷的库仑吸引或排斥。它包含在亲水计算中提高了亲水曲线预测的准确性，并将其应用扩展到更复杂的系统（即阴离子膜）。我们说明了该分析在抗菌肽的膜选择性、离子通道门控调节剂的膜分配、淀粉样蛋白 α-突触核蛋白和 Tau 以及白喉毒素和凋亡的 pH 依赖性双层相互作用的研究中的应用。抑制剂 Bcl-xL。
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