Interaction between cell penetrating peptide S4(13) and plasma membranes by molecular dynamics simulations

doi:10.7523/j.issn.2095-6134.2021.06.006

Abstract

Abstract: The derivatives of cell penetrating peptide S4(13) have been used as good drug carriers carrying nucleic acid into cells to play a therapeutic role, which has potential application value in anti-tumor targeted therapy and other fields. However, the mechanism of membrane penetration of S4(13) is still unclear. In this work, we employed molecular dynamics simulation method for study. Firstly, we built systems of single and multiple S4(13) molecules in different membrane models and aqueous solutions, respectively. Thereafter, we performed classical molecular dynamics simulations as well as umbrella sampling molecular dynamics simulations and we analyzed the trajectory to determine the means of single S4(13) and multiple S4(13) molecules with different plasma membranes. The results suggest that S4(13) binds to the bacterial plasma membrane more strongly than interacting with eukaryotic membrane in the form of a single molecule. In addition, multiple S4(13) molecules trend to aggregate to form tetramers in aqueous solution and eukaryotic model membrane. Our work investigates the mechanism of cell penetrating peptide S4(13) to penetrate membrane at the molecular level, and provides a theoretical basis for the application of S4(13) derivatives as drug carriers in the future.

Key words: S4(13), POPC membrane, POPG membrane, molecular dynamics simulations, umbrella sampling

CLC Number:

O629.72

GAO Jin, CUI Wei. Interaction between cell penetrating peptide S4(13) and plasma membranes by molecular dynamics simulations[J]. Journal of University of Chinese Academy of Sciences, 2021, 38(6): 758-771.

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