Mutual information and entropy transfer analysis employed on two inactive states of human beta‐2 adrenergic receptor (β₂‐AR) unraveled distinct communication pathways. Previously, a so‐called “highly” inactive state of the receptor was observed during 1.5 microsecond long molecular dynamics simulation where the largest intracellular loop (ICL3) was swiftly packed onto the G‐protein binding cavity, becoming entirely inaccessible. Mutual information quantifying the degree of correspondence between backbone‐C_α fluctuations was mostly shared between intra‐ and extra‐cellular loop regions in the original inactive state, but shifted to entirely different regions in this latest inactive state. Interestingly, the largest amount of mutual information was always shared among the mobile regions. Irrespective of the conformational state, polar residues always contributed more to mutual information than hydrophobic residues, and also the number of polar‐polar residue pairs shared the highest degree of mutual information compared to those incorporating hydrophobic residues. Entropy transfer, quantifying the correspondence between backbone‐C_α fluctuations at different timesteps, revealed a distinctive pathway directed from the extracellular site toward intracellular portions in this recently exposed inactive state for which the direction of information flow was the reverse of that observed in the original inactive state where the mobile ICL3 and its intracellular surroundings drove the future fluctuations of extracellular regions.

中文翻译：

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β2-肾上腺素能受体处于非活动状态的独特通信网络：互信息和熵转移分析。

互信息和对人类β-2肾上腺素能受体（β两种非活动状态中使用熵传递分析₂ -AR）拆开的不同的通信路径。以前，在1.5微秒的分子动力学模拟过程中观察到了所谓的“高度失活”受体状态，其中最大的细胞内环（ICL3）迅速堆积在G蛋白结合腔上，变得完全不可进入。互信息量化backbone-之间的对应关系的程度Ç _α波动主要在原始非活动状态的细胞内和细胞外环区域之间共享，但在最新的非活动状态下转移到完全不同的区域。有趣的是，移动区域之间始终共享最大数量的互信息。不论构象状态如何，极性残基总是比疏水性残基对互信息的贡献更大，而且极性-极性残基对的数量与掺入疏水性残基的对共享最多的互信息。熵转移，量化之间的对应backbone- Ç _α 在不同时间步长上的波动，揭示了在这种最近暴露的非活动状态下从细胞外位置指向细胞内部分的独特途径，其信息流的方向与在原始非活动状态下观察到的相反，在原始非活动状态下，移动的ICL3及其细胞内环境处于驱动状态细胞外区域的未来波动。