Department of Chemical and Biomolecular Engineering, University of Houston, Houston, Texas, USA.
Biophys J. 2010 Feb 17;98(4):586-95. doi: 10.1016/j.bpj.2009.10.046.
Using the potential of mean constrained force method, molecular dynamics simulations with atomistic details were performed to examine the partitioning and nature of interactions of two nonsteroidal antiinflammatory drugs, namely aspirin and ibuprofen, in bilayers of dipalmitoylphosphatidylcholine. Two charge states (neutral and anionic) of the drugs were simulated to understand the effect of protonation or pH on drug partitioning. Both drugs, irrespective of their charge state, were found to have high partition coefficients in the lipid bilayer from water. However, the values and trends of the free energy change and the location of the minima in the bilayer are seen to be influenced by the drug structure and charge state. In the context of the transport of the drugs through the bilayer, the charged forms were found to permeate fully hydrated in contrast to the neutral forms that permeate unhydrated.
利用平均约束力方法的潜力，通过原子细节的分子动力学模拟，研究了两种非甾体抗炎药（即阿司匹林和布洛芬）在二棕榈酰磷脂酰胆碱双层中的分配和相互作用性质。模拟了药物的两种电荷状态（中性和阴离子），以了解质子化或 pH 值对药物分配的影响。无论其电荷状态如何，两种药物在从水中分配到脂质双层时都具有高分配系数。然而，自由能变化的数值和趋势以及双层中的最小值位置都受到药物结构和电荷状态的影响。在药物通过双层运输的情况下，发现带电荷的形式可以完全穿透水合状态，而中性形式则不能穿透非水合状态。
