Modulation of glycophorin A transmembrane helix interactions by lipid bilayers: Molecular dynamics calculations
Modulation of glycophorin A transmembrane helix interactions by lipid bilayers: Molecular dynamics calculations
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DOI：
10.1006/jmbi.2000.4072
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发表时间：
2000-09-22
影响因子：
5.6
通讯作者：
Woolf, TB
中科院分区：
文献类型：
--
作者：
Petrache, HI;Grossfield, A;Woolf, TB
从核磁共振确定的糖蛋白A二聚体结构开始，我们使用CHARMM电位在恒定的常压、侧面积和温度下模拟了显性脂质双层中的二聚体和单体形式。通过对四种不同脂质的轨迹分析，揭示了脂质链长度和饱和度如何调节跨膜螺旋的结构和能量特性。螺旋倾斜、螺旋-螺旋交叉角和螺旋可达体积取决于脂质类型，其方式与疏水匹配概念一致：最相关的脂质性质似乎是双层厚度。虽然螺旋-螺旋相互作用的净焓非常吸引人，但残基-残基相互作用的分析表明，界面甘氨酸残基之间存在显著的不利静电斥力，这是二聚化的关键。在所有类型的脂质中，肽体积在二聚化时几乎是保守的，这表明单体螺旋与脂质之间的包装效果与二聚体螺旋之间的包装效果一样好。焓计算表明，当被不饱和脂溶剂化时，二聚体的螺旋-环境相互作用能比单体低。在所有脂质环境中，脂质与肽的相互作用明显倾向于主要通过一个酰基链而不是两个酰基链。虽然我们的轨迹不够长；为了进行完整的热力学处理，这些结果表明，分子动力学模拟是研究蛋白质-蛋白质、蛋白质-脂质和脂质-脂质相互作用的有力方法，这些相互作用决定了膜中跨膜α -螺旋的结构、稳定性和动力学。(C) 2000年学术出版社。
Starting from the glycophorin A dimer structure determined by NMR, we performed simulations of both dimer and monomer forms in explicit lipid bilayers with constant normal pressure, lateral area, and temperature using the CHARMM potential. Analysis of the trajectories in four different Lipids reveals how Lipid chain length and saturation modulate the structural and energetic properties of transmembrane helices. Helix tilt, helix-helix crossing angle, and helix accessible volume depend on lipid type in a manner consistent with hydrophobic matching concepts: the most relevant Lipid property appears to be the bilayer thickness. Although the net helix-helix interaction enthalpy is strongly attractive, analysis of residue-residue interactions reveals significant unfavorable electrostatic repulsion between interfacial glycine residues previously shown to be critical for dimerization. Peptide volume is nearly conserved upon dimerization in all lipid types, indicating that the monomeric helices pack equally well with lipid as dimer helices do with one another. Enthalpy calculations indicate that the helix-environment interaction energy is lower in the dimer than in the monomer form, when solvated by unsaturated lipids. In all lipid environments there is a marked preference for lipids to interact with:peptide predominantly through one rather than both acyl chains. Although our trajectories are not long enough;to allow a full thermodynamic treatment, these results demonstrate that molecular dynamics simulations are a powerful method for investigating the protein-protein, protein-lipid, and lipid-lipid interactions that determine the structure, stability and dynamics of transmembrane alpha-helices in membranes. (C) 2000 Academic Press.