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首页> 外文期刊>Biophysical Chemistry: An International Journal Devoted to the Physical Chemistry of Biological Phenomena >SIMULATION OF VOLTAGE-DEPENDENT INTERACTIONS OF ALPHA-HELICAL PEPTIDES WITH LIPID BILAYERS
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SIMULATION OF VOLTAGE-DEPENDENT INTERACTIONS OF ALPHA-HELICAL PEPTIDES WITH LIPID BILAYERS

机译:具有脂质双分子层的α-螺旋肽的电压依赖性相互作用的模拟

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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. [References: 45]
机译:通过通道形成的肽和毒素在脂质双层中形成孔被认为是依赖于电压依赖性的两亲性α-螺旋插入脂质双层中。我们已经开发出一种在CHARMm分子力学程序中使用的近似潜力,使人们可以模拟这种螺旋与脂质双层的电压依赖性相互作用。已经研究了与脂质双层相互作用的两类螺旋肽:(a)δ-毒素,一种来自金黄色葡萄球菌的26个残基形成通道的肽; (b)对应于苏云金芽孢杆菌CryIIIAδ-内毒素的孔形成域的α5和α7螺旋的合成肽。对δ-毒素分子动力学(MD)模拟的分析表明,双分子层电压的存在使δ-毒素螺旋的插入位置稳定,但本身并未引起插入。对α5和α7肽的一系列模拟显示,响应跨双分子层电压,α5螺旋在膜结合状态和膜插入状态之间动态切换。相反,α7螺旋没有显示出这种转换,而是保留了与膜相关的状态。这些结果与合成的α5和α7肽与脂质双层相互作用的最新实验研究一致。 [参考:45]

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