Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS, 66160, USA.
J Membr Biol. 2021 Feb;254(1):109-117. doi: 10.1007/s00232-021-00170-5. Epub 2021 Feb 10.
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.
水力学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。这些预测基于实验确定的疏水性尺度，为这些相互作用的倾向和稳定性提供了估计。水力学分析的准确性得到了显著提高，这要归功于流行的 Wimley-White 界面和辛醇疏水性尺度的发展。这些尺度以前已经被整合到免费的 MPEx（膜蛋白探索者）在线应用程序中。在这里，我们对 MPEx 进行了重大更新，允许考虑双层分配自由能对静电贡献的影响。这个组件源于蛋白质和膜之间的电荷的库仑吸引或排斥。将其纳入疏水性计算可提高疏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）。我们将这种分析应用于抗菌肽的膜选择性研究、离子通道门控修饰剂的膜分配以及淀粉样蛋白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。
