Orsi Mario, Sanderson Wendy E, Essex Jonathan W
School of Chemistry, University of Southampton, Southampton, SO17 1BJ United Kingdom.
J Phys Chem B. 2009 Sep 3;113(35):12019-29. doi: 10.1021/jp903248s.
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.
通过多尺度分子动力学模拟研究了八个小分子（分子量<100）有机分子跨磷脂双层的跨膜渗透。双层膜和水合水由简化、高效的粗粒度模型表示，而渗透分子则由标准的原子级力场描述。渗透性通过z约束算法的改进版本获得。通过在双层膜内选定深度处约束每个渗透物，我们对跨膜的自由能差和扩散系数进行了采样。根据非均匀溶解度-扩散模型，将这些数据结合起来，得到渗透系数。结果与先前的原子级计算和现有实验数据总体一致。在计算上，我们的多尺度方法比传统的原子级方法快两个数量级。
