Relative Affinities of Protein-Cholesterol Interactions from Equilibrium Molecular Dynamics Simulations.
Relative Affinities of Protein-Cholesterol Interactions from Equilibrium Molecular Dynamics Simulations.
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DOI：
10.1021/acs.jctc.1c00547
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发表时间：
2021-10-12
影响因子：
5.5
通讯作者：
Corey RA
中科院分区：
文献类型：
--
作者：
Ansell TB;Curran L;Horrell MR;Pipatpolkai T;Letham SC;Song W;Siebold C;Stansfeld PJ;Sansom MSP;Corey RA
脂质与膜蛋白的特定相互作用促进了蛋白质的稳定性和功能。我们开发了一种确定的方法使用结合饱和度曲线，来自平衡的粗粒型MD模拟的蛋白质 - 脂质结合率，设计用于模仿实验方案。这就是我们的结合饱和方法提供了一种可靠的高通量替代方法，用于确定在例如，在含有辅助脂质密度阵列的冷冻EM衍生的膜蛋白结构中看到的单个位点的相对结果。
Specific interactions of lipids with membrane proteins contribute to protein stability and function. Multiple lipid interactions surrounding a membrane protein are often identified in molecular dynamics (MD) simulations and are, increasingly, resolved in cryo-electron microscopy (cryo-EM) densities. Determining the relative importance of specific interaction sites is aided by determination of lipid binding affinities using experimental or simulation methods. Here, we develop a method for determining protein–lipid binding affinities from equilibrium coarse-grained MD simulations using binding saturation curves, designed to mimic experimental protocols. We apply this method to directly obtain affinities for cholesterol binding to multiple sites on a range of membrane proteins and compare our results with free energies obtained from density-based equilibrium methods and with potential of mean force calculations, getting good agreement with respect to the ranking of affinities for different sites. Thus, our binding saturation method provides a robust, high-throughput alternative for determining the relative consequence of individual sites seen in, e.g., cryo-EM derived membrane protein structures surrounded by an array of ancillary lipid densities.
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影响因子：
13.6
作者：
Corey RA;Song W;Duncan AL;Ansell TB;Sansom MSP;Stansfeld PJ
通讯作者：
Stansfeld PJ
影响因子：
16.6
作者：
Cong X;Liu Y;Liu W;Liang X;Laganowsky A
通讯作者：
Laganowsky A
影响因子：
18.2
作者：
Corradi, Valentina;Mendez-Villuendas, Eduardo;Tieleman, D. Peter
通讯作者：
Tieleman, D. Peter
影响因子：
5.5
作者：
de Jong, Djurre H.;Singh, Gurpreet;Marrink, Siewert J.
通讯作者：
Marrink, Siewert J.
影响因子：
56.9
作者：
Gong, Xin;Qian, Hongwu;Yan, Nieng
通讯作者：
Yan, Nieng