Stratum corneum (SC), the outermost layer of the skin, contains large variety of lipids, endowing them with the amphiphilic properties, needed to fulfil their key role in skin’s barrier function. The individual role of lipid types in the barrier function is difficult to understand due to the immense heterogeneity and complexity of the lipid’s organization within the SC. The lipid organization is being explored using both computational (molecular dynamics simulations) and experimental (neutron diffraction) techniques. Even though atomistic simulations provide unprecedented atomic level details, the major limitation is time and length scale that can be achieved with decent computational facility. Alternatively, coarse-grain (CG) models are currently being used to capture physics at bigger time and length scale without losing essential underlined structural information. In this study, a CG model of α-hydroxy phytosphingosines (CER[AP]) is developed based on philosophy of MARTINI force field. At first, the model is validated with various atomistic simulations and available experimental data. Later on, the model’s compatibility with other major skin lipids, cholesterol, and free fatty acid (palmitic acid) is checked by simulating a mixture of lipid multilayer in presence and absence of water. The developed model of CER[AP] is able to predict key structural properties within the acceptable error limits. The phenomena of ceramide conformation transformation, cholesterol flip-flop, and specificity of lipid arrangement within the multilayered systems is observed during the simulation. This signifies the importance of model in capturing higher order structural transformations.

中文翻译：

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皮肤脂质神经酰胺[AP]的粗粒MARTINI模型的开发和应用。

皮肤最外层的角质层（SC）包含多种脂质，赋予脂质两亲性，这些脂质必须发挥其在皮肤屏障功能中的关键作用。由于SC中脂质组织的巨大异质性和复杂性，很难理解脂质类型在屏障功能中的个体作用。正在使用计算（分子动力学模拟）和实验（中子衍射）技术来探索脂质的组织。即使原子模拟提供了前所未有的原子级详细信息，但主要的限制是时间和长度的比例，可以通过适当的计算工具来实现。或者，目前正在使用粗粒度（CG）模型在更大的时间和长度范围内捕获物理，而不会丢失基本的带下划线的结构信息。在这项研究中，基于MARTINI力场的原理，开发了一个α-羟基植物鞘氨醇（CER [AP]）的CG模型。首先，使用各种原子模拟和可用的实验数据对模型进行验证。随后，通过模拟在水存在和不存在的情况下脂质多层的混合物，检查模型与其他主要皮肤脂质，胆固醇和游离脂肪酸（棕榈酸）的相容性。CER [AP]的开发模型能够在可接受的误差范围内预测关键的结构特性。神经酰胺构象转化现象，胆固醇翻转，在模拟过程中观察到了多层系统中脂质排列的特异性。这表明模型在捕获更高阶结构转换中的重要性。