NMR-NOE and MD Simulation Study on Phospholipid Membranes : Dependence on Membrane Diameter and Multiple Time Scale Dynamics
NMR-NOE and MD Simulation Study on Phospholipid Membranes : Dependence on Membrane Diameter and Multiple Time Scale Dynamics
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磷脂膜的 NMR-NOE 和 MD 模拟研究：对膜直径和多时间尺度动力学的依赖性
DOI：
10.1021/jp204051f
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发表时间：
2011
影响因子：
3.3
通讯作者：
N.Matubayasi
中科院分区：
文献类型：
--
作者：
M.Shintani;K.Yoshida;S.Sakuraba;M.Nakahara;N.Matubayasi
利用溶液-状态1H核磁共振-核Overhauser效应(NOE)和分子动力学(MD)模拟，研究了脂膜中亲水和疏水末端基团之间的运动关联时间。将瞬时NOE方法与自旋回波法相结合，成功地应用于直径为5 nm的1-棕榈酰-溶血磷脂酰胆碱(PaLPC)胶束和直径为30~800 nm的二棕榈酰磷脂酰胆碱(DPPC)的囊泡，实现了大囊泡的1H核磁共振-NOE测量。结果表明，在∼100 nm以下，NOE强度随直径的增大而增大，在∼100 nm以上，模型膜在分子水平上被认为是平面的。对于直径较大的囊泡，虽然亲水末端和疏水末端甲基之间没有NOE，但其强度与相邻基团的NOE相当。通过对PALPC胶束和DPPC平面双层膜的分子动力学模拟，分析了位置间NOE信号的来源。即使对于亲水和疏水的末端，慢弛豫也能产生可观察到的NOE信号。由于距离和动力学信息不能单独在实验NOE中分离，因此大泡中的关联时间通过结合实验NOE强度和基于MD的距离分布来确定。对于大的囊泡，关联时间在质子位置上变化了2个数量级。这项研究表明，当与MD结合时，NOE提供了关于大小泡的动态信息，MD提供了结构信息。
Motional correlation times between the hydrophilic and hydrophobic terminal groups in lipid membranes are studied over a wide range of curvatures using the solution-state1H NMR-nuclear Overhauser effect (NOE) and molecular dynamics (MD) simulation. To enable1H NMR-NOE measurements for large vesicles, the transient NOE method is combined with the spin–echo method, and is successfully applied to a micelle of 1-palmitoyl-lysophosphatidylcholine (PaLPC) with diameter of 5 nm and to vesicles of dipalmitoylphosphatidylcholine (DPPC) with diameters ranging from 30 to 800 nm. It is found that the NOE intensity increases with the diameter up to ∼100 nm, and the model membrane is considered planar on the molecular level beyond ∼100 nm. While the NOE between the hydrophilic terminal and hydrophobic terminal methyl groups is absent for the micelle, its intensity is comparable to that for the neighboring group for vesicles with larger diameters. The origin of NOE signals between distant sites is analyzed by MD simulations of PaLPC micelles and DPPC planar bilayers. The slow relaxation is shown to yield an observable NOE signal even for the hydrophilic and hydrophobic terminal sites. Since the information on distance and dynamics cannot be separated in the experimental NOE alone, the correlation time in large vesicles is determined by combining the experimental NOE intensity and MD-based distance distribution. For large vesicles, the correlation time is found to vary by 2 orders of magnitude over the proton sites. This study shows that NOE provides dynamic information on large vesicles when combined with MD, which provides structural information.