Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, United States.
J Phys Chem B. 2013 May 2;117(17):5031-42. doi: 10.1021/jp312328n. Epub 2013 Apr 16.
To study the interaction between melittin peptides and lipid bilayer, we performed coarse-grained simulations on systems containing melittin interacting with a bilayer containing zwitterionic dipalmitoylphosphatidylcholine (DPPC) and anionic palmitoyloleoylphosphatidylglycerol (POPG) phospholipids in a 7:3 ratio. Eight different systems were considered: four at low and four at high peptide to lipid (P/L) ratios. In case of low P/L ratio we did not observe any pore creation in the bilayer. In two out of four of the simulations with the high P/L ratio, appearance of transient pores in the bilayer was observed. These pores were created due to an assembly of 3-5 melittin peptides. Not all of the peptides in the pores were in a transmembrane conformation; many of them had their termini residues anchored to the same leaflet, and these peptides assumed bent, U-shaped, conformations. We propose that when an assembly of melittin peptides creates pores, such an assembly acts as a "wedge" that splits the bilayer. To get a more detailed description of melittin on the bilayer surface and in transient pores, we performed coarse-grained to united-atom scale transformations and after that performed 50 ns molecular dynamics simulations using the united atom description of the systems. While these simulations did not show much of the change in the pore structure during the 50 ns time interval, they clearly showed the presence of water in the transient pores. The appearance of transient pores together with the translocation of peptides across the membranes is consistent with the mechanism proposed to explain graded dye leakage from large vesicles in the presence of melittin.
为了研究蜂毒素肽与脂质双层之间的相互作用，我们在含有蜂毒素与含有两性离子二棕榈酰磷脂酰胆碱（DPPC）和阴离子棕榈酰油酰磷脂酰甘油（POPG）磷脂的双层相互作用的系统中进行了粗粒化模拟，其比例为 7:3。考虑了八个不同的系统：低肽脂比（P/L）的四个系统和高肽脂比的四个系统。在低 P/L 比的情况下，我们没有观察到双层中有任何孔的形成。在高 P/L 比的四个模拟中有两个，观察到双层中出现了短暂的孔。这些孔是由于 3-5 个蜂毒素肽的组装而形成的。并非所有在孔中的肽都处于跨膜构象；它们中的许多肽的末端残基锚定在同一叶，这些肽呈现弯曲的 U 形构象。我们提出，当蜂毒素肽组装形成孔时，这种组装充当了将双层分裂的“楔子”。为了更详细地描述蜂毒素在双层表面和瞬时孔中的情况，我们进行了从粗粒化到统一原子尺度的转换，然后使用系统的统一原子描述进行了 50ns 的分子动力学模拟。虽然这些模拟在 50ns 的时间间隔内没有显示出孔结构的很大变化，但它们清楚地显示了在瞬时孔中存在水。瞬时孔的出现以及肽穿过膜的转位与提出的解释蜂毒素存在时大囊泡中染料逐渐渗漏的机制一致。
