Abstract：
Studying interactions between drugs and cell membranes is of great interest to designing novel drugs, optimizing drug delivery, and discerning drug mechanism action. In this study, we investigated the physical properties of the bilayer membrane model of POPC upon interaction with ibuprofen (IBU) using molecular dynamics simulations. The area per lipid (APL) was calculated to describe the effect of ibuprofen on the packing properties of the lipid bilayer. The APL was 0.58 nm2 and 0.63 nm2 for the membrane in low and high IBU respectively, and 0.57 nm2 for the membrane without IBU. Our finding showed that the mean square deviation (MSD) increased with increased ibuprofen content. In addition, the order parameter for the hydrocarbon chain of lipids increased with increased ibuprofen content. There was an increment in the transfer free energy after the head group region while it was maximum in the hydrophobic core for hydrogen peroxide (H2O2) (∼6.2 kcal.mol-1) and H2O (∼3.4 kcal.mol-1) which then decreased to respective values of (∼4.6 kcal.mol-1), and (∼2.3 kcal.mol-1) at the center of the bilayer in the presence of IBU. It seems that in the presence of ibuprofen, the free energy profile of the permeability of water and H2O2 significantly decreased. These findings show that ibuprofen significantly influences the physical properties of the bilayer by decreasing the packing and intermolecular interaction in the hydrocarbon chain region and increasing the water permeability of the bilayer. These results may provide insights into the local cytotoxic side effects of ibuprofen and its underlying molecular mechanisms.Communicated by Ramaswamy H. Sarma.
Ibuprofen changes the physical properties of the membrane.Ibuprofen decreases the packing and intermolecular interaction at the hydrocarbon chain of lipids.Ibuprofen increases the permeability of water and hydrogen peroxide as reactive oxygen species (ROS).Results may shed light on the local cytotoxic side effects of ibuprofen.
Ibuprofen changes the physical properties of the membrane.Ibuprofen decreases the packing and intermolecular interaction at the hydrocarbon chain of lipids.Ibuprofen increases the permeability of water and hydrogen peroxide as reactive oxygen species (ROS).Results may shed light on the local cytotoxic side effects of ibuprofen.
摘要：
研究药物与细胞膜之间的相互作用对设计新药非常有意义。优化药物输送，和辨别药物机制的作用。在这项研究中,我们使用分子动力学模拟研究了POPC与布洛芬（IBU）相互作用的双层膜模型的物理性质。计算每脂质面积(APL)以描述布洛芬对脂质双层的包装性质的影响。膜在低和高IBU中的APL分别为0.58nm2和0.63nm2。对于没有IBU的膜和0.57nm2。我们的发现表明，均方差（MSD）随着布洛芬含量的增加而增加。此外,脂质的烃链的有序参数随布洛芬含量的增加而增加。头基区域后的转移自由能增加，而过氧化氢（H2O2）的疏水核心最大（〜6.2kcal。mol-1)和H2O(~3.4千卡。mol-1)，然后降至各自的值(~4.6千卡。mol-1),和(~2.3千卡。mol-1）在IBU存在下位于双层中心。看来在布洛芬面前,水和H2O2渗透率的自由能曲线显著下降。这些发现表明布洛芬通过减少烃链区域中的堆积和分子间相互作用以及增加双层的水渗透性来显着影响双层的物理性质。这些结果可以提供对布洛芬的局部细胞毒性副作用及其潜在分子机制的见解。由RamaswamyH.Sarma沟通。
布洛芬改变膜的物理性质。布洛芬减少脂质的烃链上的堆积和分子间相互作用。布洛芬增加水和过氧化氢作为活性氧(ROS)的渗透性。结果可能揭示布洛芬的局部细胞毒性副作用。
布洛芬改变膜的物理性质。布洛芬减少脂质的烃链上的堆积和分子间相互作用。布洛芬增加水和过氧化氢作为活性氧(ROS)的渗透性。结果可能揭示布洛芬的局部细胞毒性副作用。
