New Continuum Approaches for Determining Protein-Induced Membrane Deformations
New Continuum Approaches for Determining Protein-Induced Membrane Deformations
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DOI：
10.1016/j.bpj.2017.03.040
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发表时间：
2017-05-23
影响因子：
3.4
通讯作者：
Grabe, Michael
中科院分区：
文献类型：
--
作者：
Argudo, David;Bethel, Neville P.;Grabe, Michael
膜对跨膜蛋白的影响是许多生物现象的核心，特别是牵张激活离子通道的门控。相反，膜蛋白可以影响双层，导致特定膜形状的稳定，囊泡分裂和融合期间发生的拓扑变化，以及形状依赖性蛋白质聚集。膜的连续弹性模型已被广泛用于研究蛋白质-膜相互作用。这些数学方法产生物理上可解释的膜形状，变形成本的能量估计，以及平衡配置的快照。此外，弹性模型比完全原子和粗粒度模拟方法的计算要求低得多;然而，有人认为，连续介质模型不能再现完全原子分子动力学模拟中观察到的扭曲。我们认为，这种失败可以克服使用化学和几何精确的蛋白质表示。在这里，我们提出了一个快速，可靠的混合连续原子模型，耦合蛋白质的膜。我们表明，该模型是在良好的协议与完全原子模拟的离子通道短杆菌肽嵌入在POPC膜。我们的连续计算不仅再现了由通道产生的膜扭曲，而且准确地确定了通道的方向。最后，我们使用我们的方法来研究膜弯曲周围的瞬态受体电位阳离子通道TRPV 1的充电电压传感器的作用。我们发现，膜变形显着稳定的能量TRPV 1的插入，通过暴露带电残基的S4段的解决方案。
The influence of the membrane on transmembrane proteins is central to a number of biological phenomena, notably the gating of stretch activated ion channels. Conversely, membrane proteins can influence the bilayer, leading to the stabilization of particular membrane shapes, topological changes that occur during vesicle fission and fusion, and shape-dependent protein aggregation. Continuum elastic models of the membrane have been widely used to study protein-membrane interactions. These mathematical approaches produce physically interpretable membrane shapes, energy estimates for the cost of deformation, and a snapshot of the equilibrium configuration. Moreover, elastic models are much less computationally demanding than fully atomistic and coarse-grained simulation methodologies; however, it has been argued that continuum models cannot reproduce the distortions observed in fully atomistic molecular dynamics simulations. We suggest that this failure can be overcome by using chemically and geometrically accurate representations of the protein. Here, we present a fast and reliable hybrid continuum-atomistic model that couples the protein to the membrane. We show that the model is in excellent agreement with fully atomistic simulations of the ion channel gramicidin embedded in a POPC membrane. Our continuum calculations not only reproduce the membrane distortions produced by the channel but also accurately determine the channel's orientation. Finally, we use our method to investigate the role of membrane bending around the charged voltage sensors of the transient receptor potential cation channel TRPV1. We find that membrane deformation significantly stabilizes the energy of insertion of TRPV1 by exposing charged residues on the S4 segment to solution.