Center for Bioinformatics, Saarland University, D-66041 Saarbrücken, Germany.
J Chem Phys. 2012 Oct 14;137(14):145105. doi: 10.1063/1.4757265.
A crucial process in biological cells is the translocation of newly synthesized proteins across cell membranes via integral membrane protein pores termed translocons. Recent improved techniques now allow producing artificial membranes with pores of similar dimensions of a few nm as the translocon system. For the translocon system, the protein has to be unfolded, whereas the artificial pores are wide enough so that small proteins can pass through even when folded. To study how proteins permeate through such membrane pores, we used coarse-grained Brownian dynamics simulations where the proteins were modeled as single beads or bead-spring polymers for both folded and unfolded states. The pores were modeled as cylindrical holes through the membrane with various radii and lengths. Diffusion was driven by a concentration gradient created across the porous membrane. Our results for both folded and unfolded configurations show the expected reciprocal relation between the flow rate and the pore length in agreement with an analytical solution derived by Brunn et al. [Q. J. Mech. Appl. Math. 37, 311 (1984)]. Furthermore, we find that the geometric constriction by the narrow pore leads to an accumulation of proteins at the pore entrance, which in turn compensates for the reduced diffusivity of the proteins inside the pore.
生物细胞中的一个关键过程是通过称为转位器的整膜蛋白孔将新合成的蛋白质跨膜转运。最近改进的技术现在允许生产具有与转位器系统相似尺寸的纳米级孔的人工膜。对于转位器系统，蛋白质必须展开，而人工孔足够宽，即使蛋白质折叠也可以通过。为了研究蛋白质如何通过这种膜孔渗透，我们使用粗粒布朗动力学模拟，其中蛋白质被建模为单个珠子或折叠和展开状态的珠子弹簧聚合物。孔被建模为通过膜的具有各种半径和长度的圆柱形孔。扩散是由多孔膜上的浓度梯度驱动的。我们对折叠和展开构型的结果都表明，流速与孔长度之间存在预期的倒数关系，这与 Brunn 等人推导的解析解一致[Q. J. Mech. Appl. Math. 37, 311 (1984)]。此外，我们发现窄孔的几何限制导致蛋白质在孔口处积聚，这反过来又补偿了蛋白质在孔内扩散率的降低。
