Defining the transmembrane helix of M2 protein from influenza A by molecular dynamics simulations in a lipid bilayer
Defining the transmembrane helix of M2 protein from influenza A by molecular dynamics simulations in a lipid bilayer
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DOI：
10.1016/s0006-3495(99)77347-9
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发表时间：
1999-04-01
影响因子：
3.4
通讯作者：
Sansom, MSP
中科院分区：
文献类型：
--
作者：
Forrest, LR;Tieleman, DP;Sansom, MSP
据信含有至少一个跨膜（TM）α-螺旋的整合膜蛋白占大多数基因组的20%至30%。有几种算法可以准确预测膜蛋白序列中TM螺旋的数量和位置。然而，这些方法往往不同意TM螺旋的开始和结束残基，为后续的建模和模拟研究带来了问题。在明确的脂质和水环境中的分子动力学（MD）模拟用于帮助定义来自甲型流感病毒的M2蛋白的TM螺旋。依据：比较了五种不同的二级结构预测算法的结果，模拟了三种不同的螺旋长度（18聚体、26聚体和34聚体）。每个模拟系统包含127个POPC分子加上近似3500 - 4700个沃茨，总共近似18，000 - 21，000个原子。对18聚体和26聚体进行两次模拟，每次持续2ns，并对34聚体进行五次单独的模拟，使用通过限制在真空中的MD模拟产生的不同起始模型。总模拟时间为11 ns。TM片段的时间依赖性二级结构的分析用于定义在整个模拟中采用稳定α-螺旋确认的区域。该分析表明，类似于20个残基（从残基22至残基43）的核心TM区域保持α-螺旋构象。原子密度分布的分析表明，18聚体螺旋揭示了脂质双层的局部扰动。该区域两侧的极性侧链与脂质头基和水分子形成相对长寿命的氢键。
Integral membrane proteins containing at least one transmembrane (TM) alpha-helix are believed to account for between 20% and 30% of most genomes. There are several algorithms that accurately predict the number and position of TM helices within,a membrane protein sequence. However, these methods tend to disagree over the beginning and end residues of TM helices, posing problems for subsequent modeling and simulation studies. Molecular dynamics (MD) simulations in an explicit lipid and water environment are used to help define the TM helix of the M2 protein from influenza A virus. Based on: a comparison of the results of five different secondary structure prediction algorithms, three different helix lengths (an 18mer, a 26mer, and a 34mer) were simulated. Each simulation system contained 127 POPC molecules plus similar to 3500 -4700 waters, giving a total, of similar to 18,000-21,000 atoms. Two simulations, each of 2 ns duration, were run for the 18mer and 26mer, and five separate simulations were run for the 34mer, using different starting models generated by restrained in vacuo MD simulations. The total simulation time amounted to 11 ns. Analysis of the time-dependent secondary structure of the TM segments was used to define the regions that adopted a stable alpha-helical confirmation throughout the simulation. This analysis indicates a core TM region of similar to 20 residues (from residue 22 to residue 43) that remained in an alpha-helical conformation, Analysis of atomic density profiles suggested that the 18mer helix revealed a local perturbation of the lipid bilayer. Polar side chains on either side of this region form relatively long-lived H-bonds to lipid headgroups and water molecules.