Modelling of Fibrillation Induced Selective Cytotoxicity of Phenol Soluble Modulin α3

21 January 2019, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


Phenol soluble modulin (PSM) α3, the most toxic member of α-toxin in Staphylococcus aureus bacteria, has been recently found to form cross-α 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-α3 strands, with
stabilization energy of 28.7 kCal/mol. We considered two model bilayers mimicking mammalian and bacterial cell membranes, and found that single α-helix strand penetration is energetically unfavourable 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-α3, can also act as a stepping stone in future drug development against ​S. aureus.


Amyloid alpha-peptides
PSM alpha 3
peptide bilayer interaction
free energy calculation
molecular dynamics

Supplementary materials



Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.