MEMPHYS-Centre for Biomembrane Physics, University of Southern Denmark, Odense M, Denmark.
MEMPHYS-Centre for Biomembrane Physics, University of Southern Denmark, Odense M, Denmark; Max-Planck-Institut für biophysikalische Chemie, Göttingen, Germany.
Biophys J. 2018 Apr 24;114(8):1895-1907. doi: 10.1016/j.bpj.2018.02.016.
The extent to which current force fields faithfully reproduce conformational properties of lipids in bilayer membranes, and whether these reflect the structural principles established for phospholipids in bilayer crystals, are central to biomembrane simulations. We determine the distribution of dihedral angles in palmitoyl-oleoyl phosphatidylcholine from molecular dynamics simulations of hydrated fluid bilayer membranes. We compare results from the widely used lipid force field of Berger et al. with those from the most recent C36 release of the CHARMM force field for lipids. Only the CHARMM force field produces the chain inequivalence with sn-1 as leading chain that is characteristic of glycerolipid packing in fluid bilayers. The exposure and high partial charge of the backbone carbonyls in Berger lipids leads to artifactual binding of Na ions reported in the literature. Both force fields predict coupled, near-symmetrical distributions of headgroup dihedral angles, which is compatible with models of interconverting mirror-image conformations used originally to interpret NMR order parameters. The Berger force field produces rotamer populations that correspond to the headgroup conformation found in a phosphatidylcholine lipid bilayer crystal, whereas CHARMM36 rotamer populations are closer to the more relaxed crystal conformations of phosphatidylethanolamine and glycerophosphocholine. CHARMM36 alone predicts the correct relative signs of the time-average headgroup order parameters, and reasonably reproduces the full range of NMR data from the phosphate diester to the choline methyls. There is strong motivation to seek further experimental criteria for verifying predicted conformational distributions in the choline headgroup, including the P chemical shift anisotropy and N and CD NMR quadrupole splittings.
当前力场在多大程度上忠实地再现双层膜中脂质的构象性质，以及这些性质是否反映了双层晶体中磷脂的结构原则，是生物膜模拟的核心。我们从水合流体双层膜的分子动力学模拟中确定了棕榈酰-油酰磷脂酰胆碱的二面角分布。我们将广泛使用的 Berger 等人的脂质力场的结果与最近的 C36 版本的 CHARMM 脂质力场的结果进行了比较。只有 CHARMM 力场产生了 sn-1 作为领先链的链不等效性，这是甘油脂质在流体双层中堆积的特征。Berger 脂质中骨架羰基的暴露和高部分电荷导致文献中报道的 Na 离子的人为结合。这两种力场都预测了头基二面角的耦合、近对称分布，这与最初用于解释 NMR 序参数的互变镜像构象模型兼容。Berger 力场产生的构象与在磷脂酰胆碱脂质双层晶体中发现的头基构象相对应，而 CHARMM36 构象更接近磷脂酰乙醇胺和甘油磷酸胆碱的更松弛的晶体构象。仅 CHARMM36 就预测了时间平均头基序参数的正确相对符号，并合理地再现了从磷酸二酯到胆碱甲基的全范围 NMR 数据。有强烈的动机寻求进一步的实验标准来验证胆碱头基中预测的构象分布，包括 P 化学位移各向异性和 N 和 CD NMR 四极分裂。
