Key Laboratory of Theoretical and Computational Photochemistry, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, China.
Key Laboratory of Theoretical and Computational Photochemistry, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, China.
Biophys J. 2018 Oct 16;115(8):1518-1529. doi: 10.1016/j.bpj.2018.08.040. Epub 2018 Sep 6.
This article presents coarse-grained molecular dynamics simulations of pore-forming antimicrobial peptide melittin and its interactions with vesicles composed of a mixture of zwitterionic and anionic phospholipids. Besides creating holes in the membrane, the adsorption of melittin also induces vesicle budding, which can develop into vesiculation at high peptide concentrations, as well as vesicle invagination, which can eventually result in a corrugated membrane surface. These rich morphology changes are mediated by the curvature of the vesicles and the peptide concentration. Highly curved vesicles favor the recruitment of melittins with a higher density of binding sites. The peptides mainly penetrate into the membrane surface in monomers via hydrophobic interaction. Lowly curved vesicles recruit melittins with a low density of binding sites. Surplus peptides are prone to form oligomers and shallowly adsorb on the surface of membrane via electrostatic interaction. The penetration of monomers induces membrane pore formation and positive membrane curvature, which promote vesicle budding. The adsorption of oligomers induces negative membrane curvature, which promotes vesicle invagination. This work demonstrates that antimicrobial peptides adopt multiple actions to destroy bacterial membranes.
本文对成孔抗菌肽蜂毒素及其与两性离子和阴离子混合磷脂组成的囊泡相互作用进行了粗粒化分子动力学模拟。除了在膜上打孔外,蜂毒素的吸附还诱导囊泡出芽,在高肽浓度下会发展成囊泡化,以及囊泡内陷,最终导致膜表面起皱。这些丰富的形态变化是由囊泡的曲率和肽浓度介导的。高度弯曲的囊泡有利于招募具有更高结合位点密度的蜂毒素。肽主要通过疏水相互作用以单体形式穿透膜表面。低曲率的囊泡招募具有低结合位点密度的蜂毒素。多余的肽容易形成低聚物,并通过静电相互作用在膜表面浅度吸附。单体的穿透诱导膜孔形成和正膜曲率,从而促进囊泡出芽。低聚物的吸附诱导负膜曲率,从而促进囊泡内陷。这项工作表明,抗菌肽通过多种作用破坏细菌膜。