Water Defect and Pore Formation in Atomistic and Coarse-Grained Lipid Membranes: Pushing the Limits of Coarse Graining
Water Defect and Pore Formation in Atomistic and Coarse-Grained Lipid Membranes: Pushing the Limits of Coarse Graining
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DOI：
10.1021/ct200291v
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发表时间：
2011-09-01
影响因子：
5.5
通讯作者：
Tieleman, D. Peter
中科院分区：
文献类型：
--
作者：
Bennett, W. F. Drew;Tieleman, D. Peter
脂质双层中的缺陷在一系列生物过程中是重要的，包括抗微生物肽和膜之间的相互作用、极性分子（包括药物）跨膜的运输以及从一个单层到另一个单层的脂质翻转。被动脂质翻转和极性分子跨脂质膜的易位发生在缓慢的时间尺度上，因为涉及膜中的水缺陷和孔的高能中间体。这样的缺陷是一个有趣的测试情况下，粗粒度的模型，因为它们相对较小的特征尺寸在水分子的水平和复杂的环境中的水和极性头基团在低介电膜内部。这里.我们比较粗粒度的模拟与标准的MARTINI水和两个最近开发的粗粒度极化水模型的MARTINI模型的原子模拟。虽然在某些情况下，MARTINI模型再现了正确的自由能，但原子模型和粗粒度模型之间存在结构差异。极化水模型提高了自由能，但只是适度地改善了结构。原子测试模拟中，水分子被人为地相互拴在一起，四个一组，分辨率的MARTINI，表明限制因素不是粗粒颗粒的大小，而是简单的相互作用势和/或熵在粗粒化系统中损失。通过增加吸引力的互动。在脂质的头基和水之间，我们确实观察到了孔的形成，但是以牺牲双层的正确平衡性质为代价。
Defects in lipid bilayers are important in a range of biological processes, including interactions between antimicrobial peptides and membranes, transport of polar molecules (including drugs) across membranes, and lipid flip-flop from one monolayer to the other. Passive lipid flip flop and the translocation of polar molecules across lipid membranes occur on a slow time scale because of high-energy intermediates involving water defects and pores in the membrane. Such defects are an interesting test case for coarse-grained models because of their relatively small characteristic size at the level of water molecules and the complex environment of water and polar head groups in a low-dielectric membrane interior. Here. we compare coarse-grained simulations with the MARTINI model with the standard MARTINI water and two recently developed coarse-grained polarizable water models to atomistic simulations. Although in several cases the MARTINI model reproduces the correct free energies, there are structural differences between the atomistic and coarse-grained models. The polarizable water model improves the free energies but only moderately improves the structures. Atomistic test simulations in which water molecules are artificially tethered to each other in groups of four, the resolution of MARTINI, suggest that the limiting factor is not the size of the coarse-grained particles but rather the simple interaction potential and/or the entropy lost in coarse graining the system. By increasing the attractive interaction. between the lipids' headgroup and water, we did observe pore formation but at the expense of the correct equilibrium properties of the bilayers.