Su Juanjuan, Marrink Siewert J, Melo Manuel N
Molecular Dynamics Group, Groningen Biomolecular Sciences and Biotechnology Institute and Zernike Institute for Advanced Materials, University of Groningen, Groningen, Netherlands.
Multiscale Modeling Lab, Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal.
Front Cell Dev Biol. 2020 May 19;8:350. doi: 10.3389/fcell.2020.00350. eCollection 2020.
We performed coarse-grained simulations of the antimicrobial peptides Magainin-2, BP100, MSI-103, and MSI-78 on a phase-separated membrane to study their preference for the different domains. All the peptides displayed a clear preference for the liquid-disordered (Ld) phase over the liquid-ordered (Lo) one. For BP100, MSI-103, and MSI-78 there was a further preference of the peptides for the domain interface. The peptides' preference toward the disordered phase was shown to reflect a penalization of lipid-lipid interaction enthalpy in the Lo phase, when in the vicinity of peptides. Similar results were observed at the two studied concentrations, although Ld phase saturation at the higher concentration drove some of the peptide excess to the Lo phase. Magainin-2 and MSI-103 were found to dimerize, in agreement with available experimental data. Interestingly, at high concentrations of Magainin-2 toroidal pores spontaneously formed in the Ld phase. We performed additional simulations to characterize this phenomenon, which is likely related to Magainin-2's membranolytic action.
我们在相分离膜上对抗菌肽马盖宁-2、BP100、MSI-103和MSI-78进行了粗粒度模拟，以研究它们对不同结构域的偏好。所有肽对液相无序（Ld）相的偏好明显高于液相有序（Lo）相。对于BP100、MSI-103和MSI-78，肽对结构域界面有进一步的偏好。肽对无序相的偏好表明，当肽靠近时，Lo相中脂质-脂质相互作用焓受到惩罚。在两个研究浓度下观察到类似结果，尽管较高浓度下的Ld相饱和使一些过量的肽进入Lo相。发现马盖宁-2和MSI-103会二聚化，这与现有实验数据一致。有趣的是，在高浓度的马盖宁-2作用下，Ld相中会自发形成环形孔。我们进行了额外的模拟来表征这一现象，这可能与马盖宁-2的膜溶解作用有关。
