Department of Integrative Biology and Pharmacology, University of Texas Health Science Center, Houston, Texas 77030, United States.
Frank Laboratory of Neutron Physics, Joint Institute for Nuclear Research, 141980 Dubna, Russia.
J Phys Chem B. 2020 Jun 25;124(25):5186-5200. doi: 10.1021/acs.jpcb.0c03389. Epub 2020 Jun 16.
We have determined the fluid bilayer structure of palmitoyl sphingomyelin (PSM) and stearoyl sphingomyelin (SSM) by simultaneously analyzing small-angle neutron and X-ray scattering data. Using a newly developed scattering density profile (SDP) model for sphingomyelin lipids, we report structural parameters including the area per lipid, total bilayer thickness, and hydrocarbon thickness, in addition to lipid volumes determined by densitometry. Unconstrained all-atom simulations of PSM bilayers at 55 °C using the C36 CHARMM force field produced a lipid area of 56 Å, a value that is 10% lower than the one determined experimentally by SDP analysis (61.9 Å). Furthermore, scattering form factors calculated from the unconstrained simulations were in poor agreement with experimental form factors, even though segmental order parameter () profiles calculated from the simulations were in relatively good agreement with profiles obtained from NMR experiments. Conversely, constrained area simulations at 61.9 Å resulted in good agreement between the simulation and experimental scattering form factors, but not with profiles from NMR. We discuss possible reasons for the discrepancies between these two types of data that are frequently used as validation metrics for molecular dynamics force fields.
我们通过同时分析小角度中子和 X 射线散射数据，确定了棕榈酰鞘氨醇（PSM）和硬脂酰鞘氨醇（SSM）的流体双层结构。使用新开发的鞘氨醇脂质散射密度分布（SDP）模型，我们报告了结构参数，包括脂质的单位面积、总双层厚度和烃链厚度，以及通过密度法确定的脂质体积。使用 C36 CHARMM 力场对 55°C 下的 PSM 双层进行无约束全原子模拟，得到的脂质面积为 56Å，比 SDP 分析实验确定的值低 10%（61.9Å）。此外，从无约束模拟计算得到的散射形式因子与实验形式因子相差很大，尽管从模拟计算得到的片段有序参数（S）分布与从 NMR 实验得到的 S 分布相对吻合。相反，在 61.9Å 时进行约束面积模拟可以很好地匹配模拟和实验散射形式因子，但与 NMR 得到的 S 分布不匹配。我们讨论了这些经常被用作分子动力学力场验证指标的两种类型数据之间差异的可能原因。
