Eur Biophys J. 2013 Dec;42(11-12):833-41. doi: 10.1007/s00249-013-0932-y.
In this work, we report a molecular dynamics simulations study of protonated sumatriptan (pSMT) in a fully hydrated bilayer of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidyl-choline at the fluid lamellar phase. The simulations were carried out at three different drug/lipid stoichiometries, 1:75, 1:10 and 1:3, under NPT conditions. Our results show partition of pSMT between the lipid head-water interphase and water phase. The main interactions that stabilized the systems were hydrogen bonds, salt bridges and cation-π. Besides, pSMT molecules have no access to the hydrophobic region of the bilayer at the studied concentrations. From an atomistic point of view, this work could contribute to the discussion of drug-membrane interactions regarding the limitation of sumatriptan to cross the blood-brain barrier.
在这项工作中，我们报告了质子化舒马曲坦（pSMT）在完全水合的 1-棕榈酰-2-油酰-sn-甘油-3-磷酸胆碱双层中的分子动力学模拟研究，处于流型层相。在 NPT 条件下，以三种不同的药物/脂质化学计量比，1:75、1:10 和 1:3 进行了模拟。我们的结果表明，pSMT 在脂质头部-水相间和水相之间分配。稳定系统的主要相互作用是氢键、盐桥和阳离子-π。此外，在所研究的浓度下，pSMT 分子无法进入双层的疏水区。从原子的角度来看，这项工作可能有助于讨论药物-膜相互作用，因为舒马曲坦限制了穿越血脑屏障。
