Tieleman D P, Forrest L R, Sansom M S, Berendsen H J
BIOSON Research Institute, Laboratory of Biophysical Chemistry, University of Groningen, The Netherlands.
Biochemistry. 1998 Dec 15;37(50):17554-61. doi: 10.1021/bi981802y.
Molecular dynamics simulations allow a direct study of the structure and dynamics of membrane proteins and lipids. We describe the behavior of aromatic residues and lipid properties in POPE and POPC bilayer models with the Escherichia coli OmpF trimer, single alamethicin and Influenza M2 helices, 4-helix M2 bundles, and two alamethicin 6-helix channel models. The total simulation time is over 24 ns, of systems containing solvent, protein, and between 104 and 318 lipids. Various types of adjustment between lipids and proteins occur, depending on the size of the protein and the degree of hydrophobic mismatch between lipid and protein. Single helices cause little measurable effect on nearby lipids whereas the 4-helix bundles, 6-helix channel models, and OmpF cause a significant lowering of order parameters in nearby lipid chains, an increased difference between odd and even chain dihedrals in the magnitude of the trans dihedral fractions and dihedral transition rates, and in most cases a decreased gauche population and a decrease in bilayer thickness. An increased tilt of the lipid chains near the proteins can account for most of the observed decrease in order parameters. The orientation of tryptophans and tyrosines on the outside of the proteins is determined by packing at the protein exterior and non-specific hydrogen bonding with lipids and solvent. The tyrosines in the broad bands that delimit the hydrophobic exterior of OmpF show little change in orientation over one nanosecond. Their rings are oriented predominantly perpendicular to the bilayer plane, with the hydroxyl group pointing toward the lipid-water interface. Phenylalanines in OmpF, alamethicin, and Influenza M2 are more mobile and assume a variety of orientations.
分子动力学模拟能够直接研究膜蛋白和脂质的结构与动力学。我们描述了在含有大肠杆菌OmpF三聚体、单个短杆菌肽A以及流感病毒M2螺旋、4螺旋M2束和两个短杆菌肽A 6螺旋通道模型的POPE和POPC双层模型中芳香族残基的行为和脂质特性。总模拟时间超过24纳秒，系统包含溶剂、蛋白质以及104至318个脂质。脂质和蛋白质之间会发生各种类型的调整，这取决于蛋白质的大小以及脂质与蛋白质之间疏水不匹配的程度。单个螺旋对附近脂质几乎没有可测量的影响，而4螺旋束、6螺旋通道模型和OmpF会导致附近脂质链的序参数显著降低，奇数和偶数链二面角在反式二面角分数和二面角转变速率大小上的差异增加，并且在大多数情况下，gauche构象的数量减少以及双层厚度减小。蛋白质附近脂质链倾斜度的增加可以解释观察到的序参数下降的大部分情况。蛋白质外部色氨酸和酪氨酸的取向由蛋白质外部的堆积以及与脂质和溶剂的非特异性氢键作用决定。界定OmpF疏水外部的宽带中的酪氨酸在一纳秒内取向变化很小。它们的环主要垂直于双层平面取向，羟基指向脂质 - 水界面。OmpF、短杆菌肽A和流感病毒M2中的苯丙氨酸更具流动性，并呈现出多种取向。
