Biggin P C, Sansom M S
Laboratory of Molecular Biophysics, University of Oxford, UK.
Biophys Chem. 1996 Jun 11;60(3):99-110. doi: 10.1016/0301-4622(96)00015-4.
Pore formation in lipid bilayers by channel-forming peptides and toxins is thought to follow voltage-dependent insertion of amphipathic alpha-helices into lipid bilayers. We have developed an approximate potential for use within the CHARMm molecular mechanics program which enables one to simulate voltage-dependent interaction of such helices with a lipid bilayer. Two classes of helical peptides which interact with lipid bilayers have been studied: (a) delta-toxin, a 26 residue channel-forming peptide from Staphylococcus aureus; and (b) synthetic peptides corresponding to the alpha 5 and alpha 7 helices of the pore-forming domain of Bacillus thuringiensis CryIIIA delta-endotoxin. Analysis of delta-toxin molecular dynamics (MD) simulations suggested that the presence of a transbilayer voltage stabilized the inserted location of delta-toxin helices, but did not cause insertion per se. A series of simulations for the alpha 5 and alpha 7 peptides revealed dynamic switching of the alpha 5 helix between a membrane-associated and a membrane-inserted state in response to a transbilayer voltage. In contrast the alpha 7 helix did not exhibit such switching but instead retained a membrane associated state. These results are in agreement with recent experimental studies of the interactions of synthetic alpha 5 and alpha 7 peptides with lipid bilayers.
人们认为，形成通道的肽和毒素在脂质双层中形成孔道的过程，是两亲性α-螺旋电压依赖性插入脂质双层的结果。我们已开发出一种近似势能，用于CHARMm分子力学程序，它能让人模拟此类螺旋与脂质双层的电压依赖性相互作用。研究了两类与脂质双层相互作用的螺旋肽：(a) δ-毒素，一种来自金黄色葡萄球菌的由26个残基组成的形成通道的肽；(b) 与苏云金芽孢杆菌CryIIIA δ-内毒素孔形成结构域的α5和α7螺旋对应的合成肽。对δ-毒素分子动力学（MD）模拟的分析表明，跨膜电压的存在稳定了δ-毒素螺旋的插入位置，但本身并不会导致插入。对α5和α7肽的一系列模拟显示，α5螺旋会响应跨膜电压在膜相关状态和膜插入状态之间动态切换。相比之下，α7螺旋并未表现出这种切换，而是保持膜相关状态。这些结果与最近关于合成α5和α7肽与脂质双层相互作用的实验研究结果一致。
