Polyoxyethylene glycol alkyl ether amphiphiles (C_iE_j) are important nonionic surfactants, often used for biophysical and membrane protein studies. In this work, we extensively test the GROMOS-compatible 2016H66 force field in molecular dynamics simulations involving the lamellar phase of a series of C_iE_j surfactants, namely C₁₂E₂, C₁₂E₃, C₁₂E₄, C₁₂E₅, and C₁₄E₄. The simulations reproduce qualitatively well the monitored structural properties and their experimental trends along the surfactant series, although some discrepancies remain, in particular in terms of the area per surfactant, the equilibrium phase of C₁₂E₅, and the order parameters of C₁₂E₃, C₁₂E₄, and C₁₂E₅. The polar head of the C_iE_j surfactants is highly hydrated, almost like a single polyethyleneoxide (PEO) molecule at full hydration, resulting in very compact conformations. Within the bilayer, all C_iE_j surfactants flip-flop spontaneously within tens of nanoseconds. Water-permeation is facilitated, and the bending rigidity is 4 to 5 times lower than that of typical phospholipid bilayers. In line with another recent theoretical study, the simulations show that the lamellar phase of C_iE_j contains large hydrophilic pores. These pores should be abundant in order to reproduce the comparatively low NMR order parameters. We show that their contour length is directly correlated to the order parameters, and we estimate that they should occupy approximately 7–10% of the total membrane area. Due to their highly dynamic nature (rapid flip-flops, high water permeability, observed pore formation), C_iE_j surfactant bilayers are found to represent surprisingly challenging systems in terms of modeling. Given this difficulty, the results presented here show that the 2016H66 parameters, optimized independently considering pure-liquid as well as polar and nonpolar solvation properties of small organic molecules, represent a good starting point for simulating these systems.

中文翻译：

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与GROMOS兼容的2016H66力场模拟非离子表面活性剂的双层

聚氧乙二醇烷基醚两亲物（C _i E _j）是重要的非离子表面活性剂，通常用于生物物理和膜蛋白研究。在这项工作中，我们在涉及一系列C _i E _j表面活性剂（即C ₁₂ E ₂，C ₁₂ E ₃，C ₁₂ E ₄，C _12）的层状相的分子动力学模拟中广泛测试了GROMOS兼容的2016H66力场。E ₅和C ₁₄ E ₄。模拟再现定性以及所监测的结构性能，并沿着所述表面活性剂系列的实验的趋势，虽然有些差异依然存在，特别是在每个表面活性剂的区域中，C的平衡相位方面₁₂ ë ₅，和C的顺序参数₁₂ ë ₃，C ₁₂ E ₄和C ₁₂ E ₅。C _i E _j表面活性剂的极性头高度水合，几乎就像完全水合时的单个聚环氧乙烷（PEO）分子一样，形成了非常紧凑的构象。在双层中，所有C _i E _j表面活性剂在数十纳秒内自发地翻转。促进了水的渗透，并且抗弯刚度比典型的磷脂双层的抗弯刚度低4至5倍。与最近的另一项理论研究一致，模拟表明C _i E _j的层状相包含较大的亲水孔。这些孔应该足够丰富，以便再现相对较低的NMR级参数。我们显示出它们的轮廓长度与顺序参数直接相关，并且我们估计它们应该占据膜总面积的大约7–10％。由于其高度动态的特性（快速触发器，高透水性，观察到的孔形成），C _i E _j发现表面活性剂双层在建模方面代表了令人惊讶的具有挑战性的系统。鉴于此困难，此处给出的结果表明，考虑到小有机分子的纯液体以及极性和非极性溶剂化特性而独立优化的2016H66参数代表了模拟这些系统的良好起点。