A Coarse-Grained Model of Stratum Corneum Lipids: Free Fatty Acids and Ceramide NS.
A Coarse-Grained Model of Stratum Corneum Lipids: Free Fatty Acids and Ceramide NS.
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DOI：
10.1021/acs.jpcb.6b08046
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发表时间：
2016-09-22
期刊：
影响因子：
--
通讯作者：
McCabe C
中科院分区：
文献类型：
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作者：
Moore TC;Iacovella CR;Hartkamp R;Bunge AL;McCabe C
基于神经酰胺（CER）的生物膜在实验和模拟中均用作皮肤屏障的简化模型系统。分子动力学研究通常集中在使用CER的原子详细模型来模拟预组装结构，这限制了实际上可以探测的系统大小和时间尺度，使得它们对于研究特定现象（包括自组装成双层和层状超结构）无效。在这里，我们报告了一个粗粒度（CG）模型的CER NS，最丰富的CER在人类角质层的发展。多态迭代波尔兹曼反演用于推导分子间对势，产生适用于一系列状态点且适合研究神经酰胺自组装的力场。所选择的CG映射，其中包括明确的羟基相互作用位点，捕获氢键的方向性，并允许CER NS双层的几个关键结构特性的准确预测。模拟润湿实验允许CG珠的疏水性被精确地调整以匹配原子润湿行为，这会影响整个系统，因为发现不准确的疏水特性会非物理地改变水合层状状态中的脂质包装。我们发现CER NS可以自组装成多层结构，使脂质系统的研究更能代表皮肤屏障中存在的多层脂质结构。本文推导的粗粒力场代表了使用分子动力学研究人类皮肤屏障的重要一步，这给出了仅通过实验无法获得的分辨率。
Ceramide (CER)-based biological membranes are used both experimentally and in simulations as simplified model systems of the skin barrier. Molecular dynamics studies have generally focused on simulating preassembled structures using atomistically detailed models of CERs, which limit the system sizes and timescales that can practically be probed, rendering them ineffective for studying particular phenomena, including self-assembly into bilayer and lamellar superstructures. Here, we report on the development of a coarse-grained (CG) model for CER NS, the most abundant CER in human stratum corneum. Multistate iterative Boltzmann inversion is used to derive the intermolecular pair potentials, resulting in a force field that is applicable over a range of state points and suitable for studying ceramide self-assembly. The chosen CG mapping, which includes explicit interaction sites for hydroxyl groups, captures the directional nature of hydrogen bonding and allows for accurate predictions of several key structural properties of CER NS bilayers. Simulated wetting experiments allow the hydrophobicity of CG beads to be accurately tuned to match atomistic wetting behavior, which affects the whole system since inaccurate hydrophobic character is found to unphysically alter the lipid packing in hydrated lamellar states. We find that CER NS can self-assemble into multilamellar structures, enabling the study of lipid systems more representative of the multilamellar lipid structures present in the skin barrier. The coarse-grained force field derived herein represents an important step in using molecular dynamics to study the human skin barrier, which gives a resolution not available through experiment alone.