Bilirubin, an endogenous catabolic product of the heme catabolism, can induce apoptosis in damaged cells. This study investigated the effect of bilirubin on three pro-apoptotic factors Bad, Bak, and Bim using docking and molecular dynamics simulation. Three-dimensional structures were obtained from PubChem and RCSB servers. The simulation was accomplished at 40 nanoseconds (ns) using GROMACS 2018 simulation package before docking. Then bilirubin, as a ligand, bound to these proteins by Autodock v.4.2.6 software, and molecular dynamics simulation were performed again. The hydrophobic and hydrogen bonds at the binding site were determined using LigPlot+V.4.5.3 software. Our study revealed that bilirubin has the highest tendency to bind the Bim. This binding occurred between the 10 residues at the Bim binding site with the lowest binding energy (-8.43 kcal/mol). The docking of bilirubin to Bad, Bak, and Bim decreased Total Energy (TE), increased Radius of gyration (Rg), and root-mean-square deviation (RMSD). The coil secondary structures of Bad and Bim increased significantly after docking the bilirubin. Due to exhibiting a high tendency to interact with Bad, Bak, and Bim, bilirubin can affect their molecular dynamics and increase their activity so that, apoptosis is induced in the cell, which is considered in cancer treatment.

中文翻译：

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胆红素对 Bad、Bak 和 Bim 促凋亡因子的影响：分子动力学模拟研究

胆红素是血红素分解代谢的内源性分解代谢产物，可诱导受损细胞凋亡。本研究使用对接和分子动力学模拟研究了胆红素对三种促凋亡因子 Bad、Bak 和 Bim 的影响。三维结构从 PubChem 和 RCSB 服务器获得。模拟是在对接前使用 GROMACS 2018 模拟包在 40 纳秒 (ns) 完成的。然后胆红素作为配体通过Autodock v.4.2.6软件与这些蛋白质结合，再次进行分子动力学模拟。结合位点的疏水键和氢键使用 LigPlot+V.4.5.3 软件确定。我们的研究表明，胆红素结合 Bim 的趋势最高。这种结合发生在 Bim 结合位点的 10 个残基之间，结合能最低 (-8. 43 大卡/摩尔）。胆红素与 Bad、Bak 和 Bim 的对接降低了总能量 (TE)，增加了回转半径 (Rg) 和均方根偏差 (RMSD)。Bad 和 Bim 的线圈二级结构在对接胆红素后显着增加。由于表现出与 Bad、Bak 和 Bim 相互作用的高趋势，胆红素可以影响它们的分子动力学并增加它们的活性，从而在细胞中诱导细胞凋亡，这在癌症治疗中被考虑。