Phenol soluble modulin (PSM) $\alpha$3, the most toxic member of $\alpha$-toxin in Staphylococcus aureus bacteria, forms cross-$\alpha$ amyloid fibrils and is selectively toxic to the mammalian cell membranes. In this work, it has been discovered that hydrophobic interactions play a major role in fibril formation of PSM-$\alpha$3 strands, with stabilization energy of 28.7 kCal mol^-1. We considered two model bilayers mimicking mammalian and bacterial cell membranes, and found that single $\alpha$-helix strand penetration is energetically unfavorable in both of them. Hence, we propose a simple model using energetics to understand the reason for selective toxicity of the peptide to the mammalian cell membrane. This study, besides enhancing the understanding of PSM-$\alpha$3, can also act as a stepping stone in future drug development against S. aureus.

苯酚可溶调节蛋白（PSM） $\alpha$3，最毒的成员 $\alpha$-金黄色葡萄球菌细菌中的毒素形成交叉-$\alpha$淀粉样原纤维，对哺乳动物细胞膜有选择性的毒性。在这项工作中，我们发现疏水相互作用在PSM-的原纤维形成中起主要作用$\alpha$3股，稳定能量为28.7 kCal mol ^-1。我们考虑了两个模仿哺乳动物和细菌细胞膜的双层模型，发现$\alpha$-螺旋线在两者中都在能量上不利。因此，我们提出了一个使用能量学的简单模型，以了解该肽对哺乳动物细胞膜选择性毒性的原因。这项研究除了增进对PSM的理解外，$\alpha$3，在将来针对金黄色葡萄球菌的药物开发中也可以充当垫脚石。