Multiscale Simulation of Ternary Stratum Corneum Lipid Mixtures: Effects of Cholesterol Composition.
Multiscale Simulation of Ternary Stratum Corneum Lipid Mixtures: Effects of Cholesterol Composition.
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DOI：
10.1021/acs.langmuir.2c00471
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发表时间：
2022-06-21
期刊：
影响因子：
3.9
通讯作者：
McCabe, Clare
中科院分区：
文献类型：
--
作者：
Shamaprasad, Parashara;Moore, Timothy C.;Xia, Donna;Iacovella, Christopher R.;Bunge, Annette L.;McCabe, Clare
神经酰胺N-（二十四烷酰基）-鞘氨醇（NS），胆固醇，和游离脂肪酸的混合物的分子动力学模拟进行获得分子水平的了解皮肤角质层中发现的脂质的结构。利用多状态迭代玻尔兹曼反演方法（MS-IBI），建立了胆固醇分子的粗粒力场。粗粒胆固醇力场与先前开发的神经酰胺NS，游离脂肪酸和水的粗粒力场兼容，并使用CHARMM力场对这些脂质的原子模拟进行验证。使用这些粗粒力场的多层结构的自组装模拟进行，揭示了大部分的神经酰胺采用扩展的构象，这不能发生在单一的双层水结构通常使用分子模拟研究。胆固醇流化的膜，通过促进包装缺陷和胆固醇含量的增加，发现减少双层厚度，由于增加的C24脂质尾部的交错，与实验观察一致。利用反向映射的方法，利用自组装的粗粒度多层膜系统构造了一个具有原子级分辨率的等效结构。这种原子结构的模拟结果与实验得到的中子散射长度密度分布非常吻合。在原子多层结构的内层中观察到显著的层间氢键，这在与水接触的外层或等效双层结构中未发现。这项工作突出了模拟多层结构的重要性，相比更常见的研究双层系统，使更适当的比较与多层实验膜。这些结果也提供了粗粒度的力场和多尺度模拟的框架的有效性验证。
Molecular dynamics simulations of mixtures of the ceramide N-(tetracosanoyl)-sphingosine (NS), cholesterol, and a free fatty acid are performed to gain a molecular-level understanding of the structure of the lipids found in the stratum corneum layer of skin. A new coarse-grained force field for cholesterol was developed using the multistate iterative Boltzmann inversion method (MS-IBI). The coarse-grained cholesterol force field is compatible with previously developed coarse-grained force fields for ceramide NS, free fatty acids, and water, and validated against atomistic simulations of these lipids using the CHARMM force field. Self-assembly simulations of multilayer structures using these coarse-grained force fields are performed, revealing that a large fraction of the ceramides adopt extended conformations, which cannot occur in the single bilayer in water structures typically studied using molecular simulation. Cholesterol fluidizes the membrane by promoting packing defects and an increase in cholesterol content is found to reduce the bilayer thickness, due to an increase in interdigitation of the C24 lipid tails, consistent with experimental observations. Using a reverse-mapping procedure, a self-assembled coarse-grained multilayer system is used to construct an equivalent structure with atomistic resolution. Simulations of this atomistic structure are found to closely agree with experimentally derived neutron scattering length density profiles. Significant interlayer hydrogen bonding is observed in the inner layers of the atomistic multilayer structure that are not found in the outer layers in contact with water or in equivalent bilayer structures. This work highlights the importance of simulating multilayer structures, as compared to the more commonly studied bilayer systems, to enable more appropriate comparisons with multilayer experimental membranes. These results also provide validation of the efficacy of the coarse-grained force fields and the framework for multiscale simulation.
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DOI：
10.1002/anie.202003375
发表时间：
2020-09-28
期刊：
Angewandte Chemie (International ed. in English)
影响因子：
--
作者：
Engberg O;Kováčik A;Pullmannová P;Juhaščik M;Opálka L;Huster D;Vávrová K
通讯作者：
Vávrová K
影响因子：
3.3
作者：
Farah, Karim;Fogarty, Aoife Catherine;Mueller-Plathe, Florian
通讯作者：
Mueller-Plathe, Florian
影响因子：
6.5
作者：
BOUWSTRA, JA;GOORIS, GS;BRAS, W
通讯作者：
BRAS, W
影响因子：
6.5
作者：
de Jager, MW;Gooris, GS;Bouwstra, JA
通讯作者：
Bouwstra, JA
影响因子：
2.9
作者：
HOOVER, WG
通讯作者：
HOOVER, WG