Partitioning of Nonsteroidal Antiinflammatory Drugs in Lipid Membranes: A Molecular Dynamics Simulation Study
Partitioning of Nonsteroidal Antiinflammatory Drugs in Lipid Membranes: A Molecular Dynamics Simulation Study
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DOI：
10.1016/j.bpj.2009.10.046
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发表时间：
2010-02-17
影响因子：
3.4
通讯作者：
Krishnamoorti, Ramanan
中科院分区：
文献类型：
--
作者：
Boggara, Mohan Babu;Krishnamoorti, Ramanan
采用平均约束力势方法，对两种非甾体类药物阿司匹林和布洛芬在二棕榈酰磷脂酰胆碱双层膜中的分配和相互作用进行了具有原子细节的分子动力学模拟（中性和阴离子）以理解质子化或pH对药物分配的影响。两种药物，无论它们的电荷状态如何，都被发现在脂质双层中具有高的水分配系数。自由能变化的值和趋势以及双层中最小值的位置被认为受到药物结构和电荷状态的影响。在药物通过双层的运输的背景下，发现带电形式渗透完全水合，而中性形式渗透未水合
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