Guizhou Provincial Key Laboratory of Computational Nano-Material Science, Guizhou Synergetic Innovation Center of Scientific Big Data for Advanced Manufacturing Technology , Guizhou Education University No.115, Gaoxin Road , Guiyang , Guizhou 550018 , P. R. China.
Guizhou University of Finance and Economics, School of Information , University City of Huaxi District , Guiyang , Guizhou 550025 , P. R. China.
J Phys Chem B. 2019 Sep 19;123(37):7818-7828. doi: 10.1021/acs.jpcb.9b06570. Epub 2019 Sep 9.
In our previous work, we investigated the effect of ether linkage on the physical properties of lipid bilayers using all-atom (AA) simulations with different water models. However, the influence of ether linkage on the transportation of cholesterol in lipid bilayers is less well studied. In order to reduce computational costs in simulations at large time and length scales, we present coarse-grained (CG) simulations of diphytanyl phosphatidylcholine (ether-DPhPC) and diphytanoyl phosphatidylcholine (ester-DPhPC) bilayer membranes in this work. First, the CG and AA simulations consistently show that the substitution of ether linkage for ester linkage would prevent the penetration of water into the lipid bilayer membranes. Second, it is encouraging that the CG simulations can nicely capture the ether effect on membrane dipole potential, showing that the ether substitution for ester would significantly decrease the dipole potential. In particular, the CG results agree with the AA simulation results, revealing that the change in the dipole potential is accompanied with the alteration in the orientation of linkage group. Finally, we carried out 60 μs CG simulations of ether-DPhPC and ester-DPhPC bilayers at two cholesterol concentrations (10 and 40% mole fraction, respectively), showing that the ether substitution for ester would facilitate the cholesterol flip-flop motion in lipid bilayer membranes.
在之前的工作中，我们使用不同的水模型进行全原子（AA）模拟，研究了醚键对脂质双层物理性质的影响。然而，醚键对胆固醇在脂质双层中运输的影响研究较少。为了在大时间和长度尺度的模拟中降低计算成本，我们在这项工作中提出了二植烷酰基磷脂酰胆碱（醚-DPhPC）和二植酰基磷脂酰胆碱（酯-DPhPC）双层膜的粗粒化（CG）模拟。首先，CG 和 AA 模拟一致表明，用醚键取代酯键可以防止水渗透到脂质双层膜中。其次，令人鼓舞的是，CG 模拟可以很好地捕捉到醚键对膜偶极势的影响，表明醚键取代酯键会显著降低偶极势。特别是，CG 结果与 AA 模拟结果一致，表明偶极势的变化伴随着键合基团取向的改变。最后，我们对两种胆固醇浓度（分别为 10%和 40%摩尔分数）的醚-DPhPC 和酯-DPhPC 双层膜进行了 60 μs 的 CG 模拟，结果表明，醚键取代酯键会促进胆固醇在脂质双层膜中的翻转运动。
