细胞穿膜肽S4(13)与质膜相互作用的分子动力学模拟

doi:10.7523/j.issn.2095-6134.2021.06.006

摘要/Abstract

摘要： 细胞穿膜肽S4（13）衍生物可以作为药物载体携带核酸分子进入细胞从而发挥治疗作用，在抗肿瘤靶向治疗等领域有潜在的应用价值，但其穿膜机理目前尚不明确。采用分子模拟方法，分别搭建单个及多个S4（13）在不同的质膜和水溶液中的模型，结合常规分子动力学模拟和增强采样模拟，通过轨迹分析探究单个及多个S4（13）与不同质膜的作用方式。研究结果表明：单个S4（13）分子与细菌质膜的相互作用比与真核生物质膜的更强，而在水溶液和真核生物质膜模型中，多个S4（13）分子则倾向于聚集形成四聚体，表明其穿膜机理与四聚体胶束结构有关。本项工作从分子层面上探讨了细胞穿膜肽S4（13）的穿膜机理，为S4（13）衍生物作为药物载体的应用提供了理论依据。

关键词: S4(13), POPC膜, POPG膜, 分子动力学模拟, 伞形采样

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

中图分类号:

O629.72

高金爱, 崔巍. 细胞穿膜肽S4(13)与质膜相互作用的分子动力学模拟[J]. 中国科学院大学学报, 2021, 38(6): 758-771.

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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