Atomistic Molecular Dynamics Simulations of the Interactions of Oleic and 2-Hydroxyoleic Acids with Phosphatidylcholine Bilayers
Atomistic Molecular Dynamics Simulations of the Interactions of Oleic and 2-Hydroxyoleic Acids with Phosphatidylcholine Bilayers
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DOI：
10.1021/jp203498x
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发表时间：
2011-10-13
影响因子：
3.3
通讯作者：
Ceron-Carrasco, Jose Pedro
中科院分区：
文献类型：
--
作者：
Cerezo, Javier;Zuniga, Jose;Ceron-Carrasco, Jose Pedro
据报道，脂肪油酸 (OA) 及其衍生物 2-羟基油酸 (2OHOA) 最近显示出重要的治疗活性。为了在分子和细胞水平上更好地了解这些治疗效果，在这项工作中，我们进行了分子动力学模拟，以阐明在插入浓度升高的1,2-二肉豆蔻酰-sn-甘油-3-磷酸胆碱（DMPC）和1,2-二棕榈酰-sn-甘油-3-磷酸胆碱（DPPC）双层模型中发生的结构和动力学变化。使用联合原子模型进行模拟来描述磷脂和脂肪。首先模拟了脂肪酸从水相插入双层的过程，表明这是可行的，并且可能导致双层内一定程度的相分离。然后在不同浓度的脂肪酸下模拟嵌入的均匀分散的脂肪与双层磷脂链的相互作用。这些模拟的结果表明，OA 和 2OHOA 积累至高浓度仅引起双层结构的微小变化。还观察到，随着脂肪浓度的升高，脂质和脂肪链的流动性增加，这对于脂肪酸链来说更为明显，同时双层对疏水性渗透剂的渗透性也增强。
Fatty oleic acid (OA) and, recently, its derivative 2-hydroxyoleic acid (2OHOA) have been reported to display an important therapeutic activity. To understand better these therapeutic effects at the molecular and cellular levels, in this work we have carried out molecular dynamics simulations to elucidate the structural and dynamical changes taking place in model 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) bilayers upon insertion of rising concentrations of these two fatty acids. The simulations are performed using a united-atoms model to describe both the phospholipids and the fatty adds. The process of insertion of the fatty acids from the aqueous phase into the bilayers is simulated first, showing that it is feasible and may lead to some degree of phase separation within the bilayer. The interactions of the embedded homogeneously dispersed fatty adds with the phospholipid chains of the bilayers are then simulated at different concentrations of the fatty acids. The results from these simulations show that accumulation of OA and 2OHOA up to high concentrations induces only small structural changes in the bilayers. An increase of the mobility of the lipid and fatty add chains at rising fatty add concentrations is also observed, which is more marked for the fatty acid chains, along with an enhancement of the permeability of the bilayers to the hydrophobic penetrant.