Dynamics of lipids, cholesterol, and transmembrane α-helices from microsecond molecular dynamics simulations.
Dynamics of lipids, cholesterol, and transmembrane α-helices from microsecond molecular dynamics simulations.
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DOI：
10.1021/jp507027t
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发表时间：
2014-11-26
期刊：
影响因子：
--
通讯作者：
Abrams CF
中科院分区：
文献类型：
--
作者：
Baker MK;Abrams CF
广泛的全原子分子动力学（共24 μs）允许探索构型空间和计算蛋白质嵌入的含胆固醇模型双层组分的横向扩散系数。这三种模型膜均由50/50（摩尔比）的二棕榈酰磷脂酰胆碱（DPPC）/胆固醇双层组成，并含有α-螺旋跨膜蛋白（HIV-1 gp 41 TM）。尽管胆固醇浓度高，但观察到正常的布朗运动，并且计算的扩散系数（在10-9 cm 2/s的量级上）与实验一致。扩散对各种参数敏感，恒温器伪影产生的2.4 K的温差导致扩散系数的2-10倍差异以及脂质顺序、膜厚度和单位细胞面积的显著差异。此外，特异性肽序列可能是一致观察到的一个瓣叶中更快扩散的基础。虽然这里的模拟分子动力学（MD）的数量级长于以前的研究，这三个系统没有接近遍历性。胆固醇和DPPC在肽周围的分布在微秒时间尺度上发生变化，但不足以彻底探索构型空间。这些模拟支持其他最近微秒MD的结论，甚至更长的时间尺度需要平衡模型膜和模拟更现实的细胞或病毒双层。
Extensive all-atom molecular dynamics (∼24 μs total) allowed exploration of configurational space and calculation of lateral diffusion coefficients of the components of a protein-embedded, cholesterol-containing model bilayer. The three model membranes are composed of an ∼50/50 (by mole) dipalmitoylphosphatidylcholine (DPPC)/cholesterol bilayer and contained an α-helical transmembrane protein (HIV-1 gp41 TM). Despite the high concentration of cholesterol, normal Brownian motion was observed and the calculated diffusion coefficients (on the order of 10–9 cm2/s) are consistent with experiments. Diffusion is sensitive to a variety of parameters, and a temperature difference of ∼4 K from thermostat artifacts resulted in 2–10-fold differences in diffusion coefficients and significant differences in lipid order, membrane thickness, and unit cell area. Also, the specific peptide sequence likely underlies the consistently observed faster diffusion in one leaflet. Although the simulations here present molecular dynamics (MD) an order of magnitude longer than those from previous studies, the three systems did not approach ergodicity. The distributions of cholesterol and DPPC around the peptides changed on the microsecond time scale, but not significantly enough to thoroughly explore configurational space. These simulations support conclusions of other recent microsecond MD in that even longer time scales are needed for equilibration of model membranes and simulations of more realistic cellular or viral bilayers.
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