The stabilization of the retromer protein complex can be effective in the treatment of different neurological disorders. Following the identification of bis-1,3-phenyl guanylhydrazone as an effective new compound for the treatment of amyotrophic lateral sclerosis, in this work we analyze the possible binding sites of this molecule to the VPS35/VPS29 dimer of the retromer complex. Our results show that the affinity for different sites of the protein assembly depends on compound charge and therefore slight changes in the cell microenvironment could promote different binding states. Finally, we describe a novel binding site located in a deep cleft between VPS29 and VPS35 that should be further explored to select novel molecular chaperones for the stabilization of the retromer complex.

中文翻译：

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逆转录体复合物的稳定性：双-1,3-苯基脒基腙 2a 与 VPS29/VPS35 界面的新结合位点分析

逆转录酶蛋白复合物的稳定可有效治疗不同的神经系统疾病。在鉴定双-1,3-苯基脒腙作为治疗肌萎缩侧索硬化症的有效新化合物后，在这项工作中，我们分析了该分子与逆转录体复合物的 VPS35/VPS29 二聚体的可能结合位点。我们的结果表明，蛋白质组装不同位点的亲和力取决于化合物电荷，因此细胞微环境的轻微变化可能会促进不同的结合状态。最后，我们描述了位于 VPS29 和 VPS35 之间深裂处的一个新的结合位点，应该进一步探索该结合位点以选择新的分子伴侣来稳定逆转录体复合物。