SOLUTE DIFFUSION IN LIPID BILAYER-MEMBRANES - AN ATOMIC-LEVEL STUDY BY MOLECULAR-DYNAMICS SIMULATION
SOLUTE DIFFUSION IN LIPID BILAYER-MEMBRANES - AN ATOMIC-LEVEL STUDY BY MOLECULAR-DYNAMICS SIMULATION
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DOI：
10.1021/bi00210a010
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发表时间：
1993-11-30
期刊：
影响因子：
2.9
通讯作者：
STOUCH, TR
中科院分区：
文献类型：
--
作者：
BASSOLINOKLIMAS, D;ALPER, HE;STOUCH, TR
为了阐明溶质通过脂质双层膜扩散的机制，对磷脂双层膜中的溶质进行了近 4 ns 的分子动力学模拟。该研究是脂质双层中溶质扩散的第一个原子水平研究，涉及对 Lalpha 相中完全溶剂化的二肉豆蔻酰磷脂酰胆碱 (DMPC) 双层的全原子表示进行四次模拟，以苯分子作为溶质，总计超过 7100 个原子。 这些模拟与实验证据一致，即小溶质的存在不会影响双层厚度，但会导致烃链排序的轻微扰动。在室温下，苯分子基本上具有各向同性运动并自由旋转。平移扩散速率随双层内的位置而变化，并且中心比两性离子头基附近更快，并且与双层中小溶质扩散的实验值非常一致。这些模拟阐明了双层中的扩散机制类似于气体通过软聚合物扩散的“跳跃”机制。高达 8 埃的跳跃可以在短短 5 皮秒内发生，而该时间段的平均运动仅为约 1.5 埃。在许多情况下，跳跃是通过烃链中的扭转变化来缓和的，烃链充当苯分子移动通过的空隙之间的“门”。 这些模拟与纯烷烃中苯的另一个 1000-ps 模拟的比较提供了证据，表明脂质双层不应被视为均匀的本体烃相。
To elucidate the mechanism of solute diffusion through lipid bilayer membranes, nearly 4 ns of molecular dynamics simulations of solutes in phospholipid bilayers was conducted. The study, the first atomic level study of solute diffusion in a lipid bilayer, involved four simulations of an all-atom representation of a fully solvated dimyristoylphosphatidylcholine (DMPC) bilayer in the Lalpha phase with benzene molecules as solutes, totaling over 7100 atoms. These simulations agree with experimental evidence that the presence of small solutes does not affect bilayer thickness but does result in slight perturbations in the ordering of the hydrocarbon chains. At room temperature, the benzene molecules have essentially isotropic motion and rotate freely. The rate of translational diffusion varies with position within the bilayer and is faster in the center than near the zwitterionic headgroups and is in excellent agreement with experimental values for the diffusion of small solutes in a bilayer. These simulations have elucidated the mechanism of diffusion in a bilayer to be similar to the ''hopping'' mechanism found for the diffusion of gases through soft polymers. Jumps of up to 8 angstrom can occur in as little as 5 ps whereas average motions for that time period are only approximately 1.5 angstrom. In many cases, the jumps are moderated by torsional changes in the hydrocarbon chains which serve as ''gates'' between voids through which the benzene molecules move. Comparison of these simulations with another 1000-ps simulation of benzene in a pure alkane provides evidence that lipid bilayers should not be treated as a homogeneous bulk hydrocarbon phase.