Permeability of Small Molecules through a Lipid Bilayer: A Multiscale Simulation Study
Permeability of Small Molecules through a Lipid Bilayer: A Multiscale Simulation Study
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DOI：
10.1021/jp903248s
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发表时间：
2009-09-03
影响因子：
3.3
通讯作者：
Essex, Jonathan W.
中科院分区：
文献类型：
--
作者：
Orsi, Mario;Sanderson, Wendy E.;Essex, Jonathan W.
用多尺度分子动力学模拟方法研究了8种分子量小于100的有机小分子在磷脂双层膜中的跨膜渗透。双分子层和水合水由简化的、有效的粗颗粒模型表示，而渗透分子由标准的原子级力场描述。渗透率特性通过Z约束算法的改进版本获得。通过约束每个渗透在选定的深度内的双层，我们已经采样的自由能差和扩散系数跨膜。这些数据已被合并，根据不均匀的溶解扩散模型，产生的渗透系数。结果与以前的原子水平的计算和现有的实验数据基本一致。在计算上，我们的多尺度方法比传统的原子级方法快2个数量级。
The transmembrane permeation of eight small (molecular weight < 100) organic molecules across a phospholipid bilayer is investigated by multiscale molecular dynamics simulation. The bilayer and hydrating water are represented by simplified, efficient coarse-grain models, whereas the permeating molecules are described by a standard atomic-level force-field. Permeability properties are obtained through a refined version of the z-constraint algorithm. By constraining each permeant at selected depths inside the bilayer, we have sampled free energy differences and diffusion coefficients across the membrane. These data have been combined, according to the inhomogeneous solubility-diffusion model, to yield the permeability coefficients. The results are generally consistent with previous atomic-level calculations and available experimental data. Computationally, Our multiscale approach proves 2 orders of magnitude faster than traditional atomic-level methods.