Structure of docosahexaenoic acid-containing phospholipid bilayers as studied by 2H NMR and molecular dynamics simulations
Structure of docosahexaenoic acid-containing phospholipid bilayers as studied by 2H NMR and molecular dynamics simulations
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DOI：
10.1021/ja011383j
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发表时间：
2002-01-16
影响因子：
15
通讯作者：
Brown, MF
中科院分区：
文献类型：
--
作者：
Huber, T;Rajamoorthi, K;Brown, MF
众所周知，多不饱和磷脂在必需脂肪酸的生物学功能方面很重要，例如，涉及大脑和视网膜等神经组织。在这里，我们使用了两种互补的结构方法来研究多不饱和双层脂类，即。我们的研究是首次将全原子分子动力学模拟应用于含二十二碳六烯酸(DHA；22：6 cis-Delta(4，7，10，13，16，19))的多不饱和脂类。研究了高度不饱和混链磷脂1-palmitoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine(PdPC)在液晶(L.)状态，并与不饱和程度较低的同系物1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine(POPC)进行比较。多不饱和双层膜的氢谱与不饱和程度较低的磷脂双层膜的氢谱有很大的不同，我们展示了分子动力学模拟如何结合小角X射线衍射法测定的电子密度谱来帮助解释多不饱和双层膜的复杂氢-2核磁共振谱。这项工作清楚地证明了液晶双层中多不饱和链的优先螺旋和角铁构象，这有利于链的延伸，同时保持双层的柔性。相对较长、延长的脂肪酰链的存在对于溶解完整的膜蛋白的疏水表面可能是重要的，例如视紫红质。此外，聚烯丙基DHA链有向后弯曲(发夹状)结构的趋势，这增加了每种脂类的界面面积。最后，根据双层膜对机械应力的响应分析了材料的性质。与饱和磷脂相比，含有二十二碳六烯酸的模拟磷脂双层对施加的表面张力不那么敏感，这可能意味着膜弹性(面积弹性系数，弯曲刚性)的降低。上述特征将含DHA的脂类与饱和或单不饱和脂类区分开来，可能对它们的生物学作用模式很重要。
Polyunsaturated phospholipids are known to be important with regard to the biological functions of essential fatty acids, for example, involving neural tissues such as the brain and retina. Here we have employed two complementary structural methods for the study of polyunsaturated bilayer lipids, viz. deuterium (H-2) NMR spectroscopy and molecular dynamics (MD) computer simulations Our research constitutes one of the first applications of all-atom MD simulations to polyunsaturated lipids containing docosahexaenoic acid (DHA; 22:6 cis-Delta(4,7,10,13,16,19)). Structural features of the highly unsaturated, mixed-chain phospholipid, 1-palmitoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine (PDPC), have been studied in the liquid-crystalline (L.) state and compared to the less unsaturated homolog, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC). The 2 H NMR spectra of polyunsaturated bilayers are dramatically different from those of less unsaturated phospholipid bilayers, We show how use of MD simulations can aid in interpreting the complex H-2 NMR spectra of polyunsaturated bilayers, in conjunction with electron density profiles determined from small-angle X-ray diffraction studies. This work clearly demonstrates preferred helical and angle-iron conformations of the polyunsaturated chains in liquid-crystalline bilayers, which favor chain extension while maintaining bilayer flexibility. The presence of relatively long, extended fatty acyl chains may be important for solvating the hydrophobic surfaces of integral membrane proteins, such as rhodopsin. In addition, the polyallylic DHA chains have a tendency to adopt back-bended (hairpin-like) structures, which increase the interfacial area per lipid. Finally, the material properties have been analyzed in terms of the response of the bilayer to mechanical stress. Simulated bilayers of phospholipids containing docosahexaenoic acid were less sensitive to the applied surface tension than were saturated phospholipids, possibly implying a decrease in membrane elasticity (area elastic modulus, bending rigidity). The above features distinguish DHA-containing lipids from saturated or monounsaturated lipids and may be important for their biological modes of action.