Pasenkiewicz-Gierula M, Róg T, Kitamura K, Kusumi A
Department of Biophysics, Institute of Molecular Biology, Jagiellonian University, Kraków, Poland.
Biophys J. 2000 Mar;78(3):1376-89. doi: 10.1016/S0006-3495(00)76691-4.
A molecular dynamics (MD) simulation of a fully hydrated, liquid-crystalline dimyristoylphosphatidylcholine (DMPC)-Chol bilayer membrane containing approximately 22 mol% Chol was carried out for 4.3 ns. The bilayer reached thermal equilibrium after 2.3 ns of MD simulation. A 2.0-ns trajectory generated during 2.3-4.3 ns of MD simulation was used for analyses to determine the effects of Chol on the membrane/water interfacial region. In this region, 70% of Chol molecules are linked to DMPC molecules via short-distance interactions, where the Chol hydroxyl group (OH-Chol) is 1) charge paired to methyl groups of the DMPC choline moiety ( approximately 34%), via the hydroxyl oxygen atom (Och); 2) water bridged to carbonyl ( approximately 19%) and nonester phosphate ( approximately 14%) oxygen atoms, via both Och and the hydroxyl hydrogen atom (Hch); and 3) directly hydrogen (H) bonded to carbonyl ( approximately 11%) and nonester phosphate ( approximately 5%) oxygen atoms, via Hch ( approximately 17% of DMPC-Chol links are multiple). DMPC's gamma-chain carbonyl oxygen atom is involved in 44% of water bridges and 51% of direct H bonds formed between DMPC and Chol. On average, a Chol molecule forms 0.9 links with DMPC molecules, while a DMPC molecule forms 2.2 and 0.3 links with DMPC and Chol molecules, respectively. OH-Chol makes hydrogen bonds with 1.1 water molecules, preferentially via Hch. The average number of water molecules H bonded to the DMPC headgroup is increased by 7% in the presence of Chol. These results indicate that inclusion of Chol decreases interlipid links and increases hydration in the polar region of the membrane.
对含有约22摩尔%胆固醇（Chol）的完全水合的液晶二肉豆蔻酰磷脂酰胆碱（DMPC）-Chol双层膜进行了4.3纳秒的分子动力学（MD）模拟。在MD模拟2.3纳秒后，双层膜达到热平衡。使用在MD模拟2.3 - 4.3纳秒期间生成的2.0纳秒轨迹进行分析，以确定Chol对膜/水界面区域的影响。在该区域，70%的Chol分子通过短程相互作用与DMPC分子相连，其中Chol羟基（OH-Chol）：1）通过羟基氧原子（Och）与DMPC胆碱部分的甲基形成电荷配对（约34%）；2）通过Och和羟基氢原子（Hch）与羰基（约19%）和非酯磷酸（约14%）氧原子形成水桥；3）通过Hch直接与羰基（约11%）和非酯磷酸（约5%）氧原子形成氢键（约17%的DMPC-Chol连接是多重的）。DMPC的γ链羰基氧原子参与了DMPC和Chol之间形成的44%的水桥和51%的直接氢键。平均而言，一个Chol分子与DMPC分子形成0.9个连接，而一个DMPC分子分别与DMPC和Chol分子形成2.2个和0.3个连接。OH-Chol优先通过Hch与1.1个水分子形成氢键。在存在Chol的情况下，与DMPC头部基团形成氢键的水分子平均数量增加了7%。这些结果表明，Chol的加入减少了脂质间连接，并增加了膜极性区域的水合作用。
