Irudayam Sheeba J, Berkowitz Max L
Department of Chemistry, University of North Carolina at Chapel Hill, North Carolina, NC 27599, USA.
Biochim Biophys Acta. 2012 Dec;1818(12):2975-81. doi: 10.1016/j.bbamem.2012.07.026. Epub 2012 Aug 2.
We performed, using an all-atom force field, molecular dynamics computer simulations to study the binding of melittin to the POPC bilayer and its subsequent reorientation in this bilayer. The binding process involves a simultaneous folding and adsorption of the peptide to the bilayer, followed by the creation of a "U shaped" conformation. The reorientation of melittin from the parallel to the perpendicular conformation requires charged residues to cross the hydrophobic core of the bilayer. This is accomplished by a creation of defects in the bilayer that are filled out with water. The defects are caused by peptide charged residues dragging the lipid headgroup atoms along with them, as they reorient. With increased concentration of melittin water defects form stable pores; this makes it easier for the peptide N-terminus to reorient. Our results complement experimental and computational observations of the melittin/lipid bilayer interaction.
我们使用全原子力场进行了分子动力学计算机模拟，以研究蜂毒肽与1-棕榈酰-2-油酰-sn-甘油-3-磷酸胆碱（POPC）双层膜的结合及其在该双层膜中的后续重排。结合过程涉及肽段同时折叠并吸附到双层膜上，随后形成“U形”构象。蜂毒肽从平行构象重排为垂直构象需要带电残基穿过双层膜的疏水核心。这是通过在双层膜中形成用水填充的缺陷来实现的。这些缺陷是由肽段带电残基在重排时拖动脂质头部基团原子引起的。随着蜂毒肽浓度的增加，水缺陷形成稳定的孔；这使得肽段的N端更容易重排。我们的结果补充了蜂毒肽/脂质双层膜相互作用的实验和计算观察结果。
