SIMULATION OF WATER TRANSPORT THROUGH A LIPID-MEMBRANE
SIMULATION OF WATER TRANSPORT THROUGH A LIPID-MEMBRANE
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DOI：
10.1021/j100066a040
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发表时间：
1994-04-14
影响因子：
--
通讯作者：
BERENDSEN, HJC
中科院分区：
文献类型：
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作者：
MARRINK, SJ;BERENDSEN, HJC
为了深入了解水透过脂膜的过程，我们对磷脂(DPPC)/水体系进行了原子细节的分子动力学模拟。由于实际的渗透过程太慢，不能直接研究，我们通过计算水分子在双层中的自由能和扩散速率分布，间接地推导出渗透速率。我们的结论是，水通过脂膜的渗透不能用简单的均相溶解扩散模型来描述。由于膜的不均匀性质，过剩自由能和扩散速率都强烈地依赖于膜中的位置。计算得到的超额自由能分布斜率较浅，最大高度为26kJ/mol。膜中部的扩散速率最大，膜脂密度较低。在界面区域，几乎所有的水分子都被脂头基团结合，扩散被证明是小一个数量级的。总输运过程本质上是由自由能垒决定的。限速步骤是通过脂尾的致密部分渗透，在那里阻力最高。我们发现在350K时的渗透速率为7(+/-3)×10(-2)cm/S，如果根据模拟温度进行校正，则与DPPC膜的实验值相当。考虑到膜的非均质性，我们定义了一个新的“四区”模型，该模型似乎比“两相”溶解扩散模型更接近实际。
To obtain insight in the process of water permeation through a lipid membrane, we performed molecular dynamics simulations on a phospholipid (DPPC)/water system with atomic detail. Since the actual process of permeation is too slow to be studied directly, we deduced the permeation rate indirectly via computation of the free energy and diffusion rate profiles of a water molecule across the bilayer. We conclude that the permeation of water through a lipid membrane cannot be described adequately by a simple homogeneous solubility-diffusion model. Both the excess free energy and the diffusion rate strongly depend on the position in the membrane, as a result from the inhomogeneous nature of the membrane. The calculated excess free energy profile has a shallow slope and a maximum height of 26 kJ/mol. The diffusion rate is highest in the middle of the membrane where the lipid density is low. In the interfacial region almost all water molecules are bound by the lipid headgroups, and the diffusion turns out to be 1 order of magnitude smaller. The total transport process is essentially determined by the free energy barrier. The rate-limiting step is the permeation through the dense part of the lipid tails, where the resistance is highest. We found a permeation rate of 7(+/-3) x 10(-2) cm/s at 350 K, comparable to experimental values for DPPC membranes, if corrected for the temperature of the simulation. Taking the inhomogeneity of the membrane into account, we define a new ''four-region'' model which seems to be more realistic than the ''two-phase'' solubility-diffusion model.