Supported lipid bilayers are an abundant research platform for understanding the behavior of real cell membranes as they allow for additional mechanical stability and at the same time have a fundamental structure approximating cell membranes. However, in computer simulations these systems have been studied only rarely up to now. An important property, which cannot be easily determined by molecular dynamics or experiments, is the unsymmetrical density profiles of bilayer leaflets density imbalance inflicted on the membrane by the support. This imbalance in the leaflets composition has consequences for membrane structure and phase behavior, and therefore we need to understand it in detail. The free energy can be used to determine the equilibrium structure of a given system. We employ an umbrella sampling approach to obtain the free energy of a lipid crossing the membrane i.e., lipid flip-flop as a function of bilayer composition and hence the equilibrium composition of the supported bilayers. In this paper, we use a variant of the coarse-grained Martini model. The results of the free energy calculation lead to a 5% higher density in the proximal leaflet. Recent data obtained by large scale modeling using a water free model suggested that the proximal leaflet had 3.2% more lipids than the distal leaflet Hoopes et al., J. Chem. Phys. 129, 175102 2008. Our findings are in line with these results. We compare results of the free energy of transport obtained by pulling the lipid across the membrane in different ways. There are small quantitative differences, but the overall picture is consistent. We additionally characterize the intermediate states, which determine the barrier height and therefore the rate of translocation. Calculations on unsupported bilayers are used to validate the approach and to determine the barrier to flip-flop in a free membrane.
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机译：支持的脂质双层是了解真实细胞膜行为的丰富研究平台，因为它们可以提供额外的机械稳定性，同时具有近似于细胞膜的基本结构。但是，到目前为止，在计算机仿真中很少研究这些系统。分子动力学或实验无法轻易确定的重要特性是支撑体在膜上造成的双层小叶密度不平衡的不对称密度分布。小叶成分的这种不平衡对膜结构和相行为有影响，因此我们需要详细了解它。自由能可用于确定给定系统的平衡结构。我们采用伞式采样方法来获得穿过膜的脂质的自由能，即脂质翻转随双层组成的函数，并因此取决于所支撑的双层的平衡组成。在本文中，我们使用了粗粒度马提尼模型的一种变体。自由能计算的结果导致近端小叶中的密度增加了5％。通过使用无水模型的大规模建模获得的最新数据表明，近端小叶的脂质比远端小叶的多3.2％Hoopes et al。，J. Chem。物理129，1751022008。我们的发现与这些结果一致。我们比较了通过以不同方式将脂质拉过膜而获得的运输自由能的结果。数量上的差异很小，但总体情况是一致的。我们还表征了中间状态，这些状态决定了势垒高度并因此决定了易位率。使用无支撑双层的计算来验证该方法并确定自由膜中翻转的障碍。
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