Experimental validation of molecular dynamics simulations of lipid bilayers:: A new approach
Experimental validation of molecular dynamics simulations of lipid bilayers:: A new approach
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DOI：
10.1529/biophysj.104.046821
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发表时间：
2005-02-01
影响因子：
3.4
通讯作者：
White, SH
中科院分区：
文献类型：
--
作者：
Benz, RW;Castro-Román, F;White, SH
一种新的方案已被开发出来，用于比较通过模拟确定的脂质双层结构特性与通过衍射实验确定的结构特性，这使得严格测试分子动力学模拟重现实验数据的能力成为可能。这种与模型无关的方法包括以分析实验数据相同的方式分析来自分子动力学双层模拟的数据，即确定系统的结构因子，并通过傅里叶重构得到整体的跨双层散射密度分布。分别使用联合原子的GROMACS和全原子的CHARMM22/27力场以及GROMACS和NAMD软件包，在恒压恒温系综中对相对湿度为66%（5.4个水分子/脂质）的二油酰磷脂酰胆碱双层进行了多纳秒的分子动力学模拟。通过比较模拟结果与实验结果，对模拟的双层结构质量进行了评估，比较的方面包括双层厚度、面积/脂质、单个分子成分分布、连续和离散结构因子以及整体散射密度分布。GROMACS和CHARMM22/27模拟都没有在实验误差范围内重现实验数据。模拟的末端甲基分布宽度与实验观察到的分布显示出特别大的差异。对较旧的CHARMM22和较新的CHARMM27力场的比较表明，在开发用于经验性描述脂质双层系统的原子力场方面正在取得重大进展。
A novel protocol has been developed for comparing the structural properties of lipid bilayers determined by simulation with those determined by diffraction experiments, which makes it possible to test critically the ability of molecular dynamics simulations to reproduce experimental data. This model-independent method consists of analyzing data from molecular dynamics bilayer simulations in the same way as experimental data by determining the structure factors of the system and, via Fourier reconstruction, the overall transbilayer scattering-density profiles. Multi-nanosecond molecular dynamics simulations of a dioleoylphosphatidylcholine bilayer at 66% RH (5.4 waters/lipid) were performed in the constant pressure and temperature ensemble using the united-atom GROMACS and the all-atom CHARMM22/27 force fields with the GROMACS and NAMD software packages, respectively. The quality of the simulated bilayer structures was evaluated by comparing simulation with experimental results for bilayer thickness, area/lipid, individual molecular-component distributions, continuous and discrete structure factors, and overall scattering-density profiles. Neither the GROMACS nor the CHARMM22/27 simulations reproduced experimental data within experimental error. The widths of the simulated terminal methyl distributions showed a particularly strong disagreement with the experimentally observed distributions. A comparison of the older CHARMM22 with the newer CHARMM27 force fields shows that significant progress is being made in the development of atomic force fields for describing lipid bilayer systems empirically.