Park Soohyung, Beaven Andrew H, Klauda Jeffery B, Im Wonpil
Department of Chemical and Biomolecular Engineering and the Biophysics Program, University of Maryland , College Park, Maryland 20742, United States.
J Chem Theory Comput. 2015 Jul 14;11(7):3466-77. doi: 10.1021/acs.jctc.5b00232.
Difficulties in estimating the correct number of lipids in each leaflet of complex bilayer membrane simulation systems make it inevitable to introduce a mismatch in lipid packing (i.e., area per lipid) and thus alter the lateral pressure of each leaflet. To investigate potential impacts of such mismatch on simulation results, we performed molecular dynamics simulations of saturated and monounsaturated lipid bilayers with and without gramicidin A or WALP23 at various mismatches by adjusting the number of lipids in the lower leaflet from no mismatch to a 25% reduction compared to that in the upper leaflet. All simulations were stable under the constant pressure barostat, but the mismatch induces asymmetric lipid packing between the leaflets, so that the upper leaflet becomes more ordered, and the lower leaflet becomes less ordered. The mismatch impacts on various bilayer properties are mild up to 5-10% mismatch, and bilayers with fully saturated chains appear to be more prone to these impacts than those with unsaturated tails. The nonvanishing leaflet surface tensions and the free energy derivatives with respect to the bilayer curvature indicate that the bilayer would be energetically unstable in the presence of mismatch. We propose a quantitative criterion for allowable mismatch based on the energetics derived from a continuum elastic model, which grows as a square root of the number of the lipids in the system. On the basis of this criterion, we infer that the area per lipid mismatch up to 5% would be tolerable in various membrane simulations of reasonable all-atom system sizes (40-160 lipids per leaflet).
在复杂双层膜模拟系统中，估算每个小叶中脂质的正确数量存在困难，这使得不可避免地会引入脂质堆积的不匹配（即每个脂质的面积），从而改变每个小叶的侧向压力。为了研究这种不匹配对模拟结果的潜在影响，我们通过将下层小叶中的脂质数量从不匹配调整为比上层小叶减少25%，对有和没有短杆菌肽A或WALP23的饱和和单不饱和脂质双层在各种不匹配情况下进行了分子动力学模拟。在恒压恒温器下所有模拟都是稳定的，但这种不匹配会导致小叶之间脂质堆积不对称，使得上层小叶变得更有序，而下层小叶变得更无序。在不匹配达到5 - 10%之前，对各种双层膜特性的影响较小，并且具有完全饱和链的双层膜似乎比具有不饱和尾部的双层膜更容易受到这些影响。小叶表面张力和相对于双层膜曲率的自由能导数不为零，这表明在存在不匹配的情况下双层膜在能量上是不稳定的。我们基于从连续弹性模型导出的能量学提出了一个允许不匹配的定量标准，该标准随着系统中脂质数量的平方根而增长。基于这个标准，我们推断在合理的全原子系统尺寸（每个小叶40 - 160个脂质）的各种膜模拟中，每个脂质的面积不匹配高达5%是可以容忍的。
