Department of Physics, Tampere University of Technology, Tampere, Finland.
Biophys J. 2011 Apr 6;100(7):1651-9. doi: 10.1016/j.bpj.2011.02.027.
Increasing experimental evidence has shown that membrane protein functionality depends on molecular composition of cell membranes. However, the origin of this dependence is not fully understood. It is reasonable to assume that specific lipid-protein interactions are important, yet more generic effects due to mechanical properties of lipid bilayers likely play a significant role too. Previously it has been demonstrated using models for elastic properties of membranes and lateral pressure profiles of lipid bilayers that the mechanical properties of a lipid bilayer can contribute as much as ∼10 k(B)T to the free energy difference associated with a change in protein conformational state. Here, we extend those previous approaches to a more realistic model for a large mechanosensitive channel (MscL). We use molecular dynamics together with the MARTINI model to simulate the open and closed states of MscL embedded in a DOPC bilayer. We introduce a procedure to calculate the mechanical energy change in the channel gating using a three-dimensional pressure distribution inside a membrane, computed from the molecular dynamics simulations. We decompose the mechanical energy to terms associated with area dilation and shape contribution. Our results highlight that the lateral pressure profile of a lipid bilayer together with the shape change in gating can induce a contribution of ∼30 k(B)T on the gating energy of MscL. This contribution arises largely from the interfacial tension between hydrophobic and hydrophilic regions in a lipid bilayer.
越来越多的实验证据表明，膜蛋白的功能取决于细胞膜的分子组成。然而，这种依赖性的起源还不完全清楚。可以合理地假设特定的脂质-蛋白质相互作用很重要，但由于脂质双层的力学性质，更一般的效应可能也起着重要的作用。以前已经使用膜的弹性性质模型和脂质双层的侧向压力分布模型证明，脂质双层的力学性质可以对与蛋白质构象状态变化相关的自由能差贡献高达约 10 k(B)T。在这里，我们将这些先前的方法扩展到一个更现实的大机械敏感通道（MscL）模型。我们使用分子动力学和 MARTINI 模型来模拟嵌入 DOPC 双层中的 MscL 的开放和关闭状态。我们引入了一种使用膜内的三维压力分布来计算通道门控过程中机械能变化的方法，该压力分布是通过分子动力学模拟计算得到的。我们将机械能分解为与面积扩张和形状贡献相关的项。我们的结果强调，脂质双层的侧向压力分布以及门控过程中的形状变化可以导致 MscL 的门控能量贡献约 30 k(B)T。这种贡献主要来自于脂质双层中疏水区和亲水区之间的界面张力。
