Expanding MPEx Hydropathy Analysis to Account for Electrostatic Contributions to Protein Interactions with Anionic Membranes.
Expanding MPEx Hydropathy Analysis to Account for Electrostatic Contributions to Protein Interactions with Anionic Membranes.
复制标题
扩展MPEX亲水性分析以解释蛋白质与阴离子膜相互作用的静电贡献。
DOI：
10.1007/s00232-021-00170-5
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Ladokhin AS
中科院分区：
文献类型：
--
作者：
Vasquez-Montes V;Ladokhin AS
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。预测是基于实验确定的疏水性尺度，这提供了这些相互作用的倾向和稳定性的估计。通过流行的Wimley-White界面和辛醇疏水性量表的发展，亲水性分析的准确性得到了显着提高。这些量表之前已整合到免费提供的MPEx（膜蛋白探索者）在线应用程序中。在这里，我们介绍了一个实质性的更新MPEX，允许考虑静电贡献的双层分区自由能。该组分源自蛋白质和膜之间电荷的库仑吸引或排斥。将其包含在亲水性计算中增加了亲水性图预测的准确性，并将其应用扩展到更复杂的系统（即，阴离子膜）。我们说明了这种分析的应用，抗菌肽的膜选择性的研究，离子通道门控修饰剂的膜分区，和淀粉样蛋白α-突触核蛋白和Tau，以及白喉毒素和凋亡抑制剂Bcl-xL的pH依赖性双层相互作用。
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.
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影响因子：
2.4
作者：
Fernandez-Vidal, Monica;White, Stephen H.;Ladokhin, Alexey S.
通讯作者：
Ladokhin, Alexey S.
影响因子：
2.9
作者：
MATSUZAKI, K;SUGISHITA, K;MIYAJIMA, K
通讯作者：
MIYAJIMA, K
影响因子：
5.6
作者：
Ladokhin, AS;White, SH
通讯作者：
White, SH
影响因子：
4.8
作者：
Murray, D;McLaughlin, S;Honig, B
通讯作者：
Honig, B
影响因子：
2.4
作者：
Chen, Charles H.;Starr, Charles G.;Ulmschneider, Jakob P.
通讯作者：
Ulmschneider, Jakob P.