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Transmembrane Pore Structures of β-Hairpin Antimicrobial Peptides by All-Atom Simulations
The Journal of Physical Chemistry B ( IF 2.8 ) Pub Date : 2017-09-21 00:00:00 , DOI: 10.1021/acs.jpcb.7b06591 Richard Lipkin 1, 2 , Almudena Pino-Angeles 1 , Themis Lazaridis 1
The Journal of Physical Chemistry B ( IF 2.8 ) Pub Date : 2017-09-21 00:00:00 , DOI: 10.1021/acs.jpcb.7b06591 Richard Lipkin 1, 2 , Almudena Pino-Angeles 1 , Themis Lazaridis 1
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Protegrin-1 is an 18-residue β-hairpin antimicrobial peptide (AMP) that has been suggested to form transmembrane β-barrels in biological membranes. However, alternative structures have also been proposed. Here, we performed multimicrosecond, all-atom molecular dynamics simulations of various protegrin-1 oligomers on the membrane surface and in transmembrane topologies. The membrane surface simulations indicated that protegrin dimers are stable, whereas trimers and tetramers break down. Tetrameric arcs remained stably inserted in lipid membranes, but the pore water was displaced by lipid molecules. Unsheared protegrin β-barrels opened into β-sheets that surrounded stable aqueous pores, whereas tilted barrels with sheared hydrogen bonding patterns were stable in most topologies. A third type of observed pore consisted of multiple small oligomers surrounding a small, partially lipidic pore. We also considered the β-hairpin AMP tachyplesin, which showed less tendency to oligomerize than protegrin: the octameric bundle resulted in small pores surrounded by six peptides as monomers and dimers, with some peptides returning to the membrane surface. The results imply that multiple configurations of protegrin oligomers may produce aqueous pores and illustrate the relationship between topology and putative steps in protegrin-1’s pore formation. However, the long-term stability of these structures needs to be assessed further.
中文翻译：
全原子模拟β-发夹抗菌肽的跨膜孔结构
Protegrin-1是18个残基的β-发夹式抗菌肽（AMP），已被建议在生物膜中形成跨膜β-桶。但是，还提出了替代结构。在这里，我们在膜表面和跨膜拓扑中进行了多种protegrin-1低聚物的多微秒全原子分子动力学模拟。膜表面模拟表明，protegrin二聚体稳定，而三聚体和四聚体分解。四聚体弧保持稳定地插入脂质膜中，但是孔隙水被脂质分子置换。未剪切的protegrinβ桶打开成包围稳定水孔的β片状结构，而在大多数拓扑结构中，带有剪切氢键模式的倾斜桶是稳定的。第三类观察到的孔由包围小的部分脂质孔的多个小低聚物组成。我们还考虑了β-发夹AMP速激肽，其寡聚化的趋势低于protegrin：八聚体束产生的小孔被六种作为单体和二聚体的肽包围，有些肽返回到膜表面。结果表明，protegrin-1低聚物的多种构型可能产生水孔，并说明了protegrin-1孔形成中拓扑结构与推定步骤之间的关系。但是，这些结构的长期稳定性需要进一步评估。八聚体束产生的小孔被六种作为单体和二聚体的肽包围，有些肽返回到膜表面。结果表明，protegrin-1低聚物的多种构型可能产生水孔，并说明了protegrin-1孔形成中拓扑结构与推定步骤之间的关系。但是，这些结构的长期稳定性需要进一步评估。八聚体束产生的小孔被六种作为单体和二聚体的肽包围，其中一些肽返回到膜表面。结果表明，protegrin-1低聚物的多种构型可能产生水孔，并说明了protegrin-1孔形成中拓扑结构与推定步骤之间的关系。但是，这些结构的长期稳定性需要进一步评估。
更新日期：2017-09-21
中文翻译：
全原子模拟β-发夹抗菌肽的跨膜孔结构
Protegrin-1是18个残基的β-发夹式抗菌肽（AMP），已被建议在生物膜中形成跨膜β-桶。但是，还提出了替代结构。在这里，我们在膜表面和跨膜拓扑中进行了多种protegrin-1低聚物的多微秒全原子分子动力学模拟。膜表面模拟表明，protegrin二聚体稳定，而三聚体和四聚体分解。四聚体弧保持稳定地插入脂质膜中，但是孔隙水被脂质分子置换。未剪切的protegrinβ桶打开成包围稳定水孔的β片状结构，而在大多数拓扑结构中，带有剪切氢键模式的倾斜桶是稳定的。第三类观察到的孔由包围小的部分脂质孔的多个小低聚物组成。我们还考虑了β-发夹AMP速激肽，其寡聚化的趋势低于protegrin：八聚体束产生的小孔被六种作为单体和二聚体的肽包围，有些肽返回到膜表面。结果表明，protegrin-1低聚物的多种构型可能产生水孔，并说明了protegrin-1孔形成中拓扑结构与推定步骤之间的关系。但是，这些结构的长期稳定性需要进一步评估。八聚体束产生的小孔被六种作为单体和二聚体的肽包围，有些肽返回到膜表面。结果表明，protegrin-1低聚物的多种构型可能产生水孔，并说明了protegrin-1孔形成中拓扑结构与推定步骤之间的关系。但是，这些结构的长期稳定性需要进一步评估。八聚体束产生的小孔被六种作为单体和二聚体的肽包围，其中一些肽返回到膜表面。结果表明，protegrin-1低聚物的多种构型可能产生水孔，并说明了protegrin-1孔形成中拓扑结构与推定步骤之间的关系。但是，这些结构的长期稳定性需要进一步评估。
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