La Rocca P, Shai Y, Sansom M S
Department of Biochemistry, University of Oxford, UK.
Biophys Chem. 1999 Feb 1;76(2):145-59. doi: 10.1016/s0301-4622(98)00232-4.
Dermaseptins, a family of antimicrobial peptides, are believed to act by forming amphipathic alpha-helices which associate with the cell membrane, leading to its permeabilisation and disruption. A simple mean field method is described for simulation of the interactions of peptides with lipid bilayers which includes an approximate representation of the electrostatic effects of the head-group region of the bilayer. Starting from an atomistic model of a PC phospholipid bilayer we calculate an average electrostatic potential along the bilayer normal. By combining the interaction of the peptide with this electrostatic potential and with the hydrophobic core of the membrane we arrive at a more complete description of peptide-bilayer energetics than would be obtained using sidechain hydrophobicities alone. Using this interaction potential in MD simulations of the frog skin peptide dermaseptin B reveals that the lipid bilayer stabilises the alpha-helical conformation of the peptide. This is in agreement with FTIR data. A surface associated orientation thus appears to be the most stable arrangement of the peptide, at least at zero ionic strength and without taking account of possible peptide-peptide interactions.
皮肤防御素是一类抗菌肽，据信其作用机制是形成两亲性α-螺旋，这些螺旋与细胞膜结合，导致细胞膜通透性增加并被破坏。本文描述了一种简单的平均场方法，用于模拟肽与脂质双层的相互作用，该方法包括对双层头部区域静电效应的近似表示。从PC磷脂双层的原子模型出发，我们计算了沿双层法线方向的平均静电势。通过将肽与这种静电势以及膜的疏水核心的相互作用相结合，我们得到了比仅使用侧链疏水性更完整的肽-双层能量学描述。在青蛙皮肤肽皮肤防御素B的分子动力学模拟中使用这种相互作用势表明，脂质双层稳定了肽的α-螺旋构象。这与傅里叶变换红外光谱（FTIR）数据一致。因此，至少在零离子强度且不考虑可能的肽-肽相互作用的情况下，表面相关取向似乎是肽最稳定的排列方式。
