Polyansky Anton A, Volynsky Pavel E, Nolde Dmitry E, Arseniev Alexander S, Efremov Roman G
Department of Bioengineering, Biological Faculty, M. V. Lomonosov Moscow State University, Moscow 119992, Russia.
J Phys Chem B. 2005 Aug 11;109(31):15052-9. doi: 10.1021/jp0510185.
Anionic unsaturated lipid bilayers represent suitable model systems that mimic real cell membranes: they are fluid and possess a negative surface charge. Understanding of detailed molecular organization of water-lipid interfaces in such systems may provide an important insight into the mechanisms of proteins' binding to membranes. Molecular dynamics (MD) of full-atom hydrated lipid bilayers is one of the most powerful tools to address this problem in silico. Unfortunately, wide application of computational methods for such systems is limited by serious technical problems. They are mainly related to correct treatment of long-range electrostatic effects. In this study a physically reliable model of an anionic unsaturated bilayer of 1,2-dioleoyl-sn-glycero-3-phosphoserine (DOPS) was elaborated and subjected to long-term MD simulations. Electrostatic interactions were treated with two different algorithms: spherical cutoff function and particle-mesh Ewald summation (PME). To understand the role of lipid charge in the system behavior, similar calculations were also carried out for zwitterionic bilayer composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). It was shown that, for the charged DOPS bilayer, the PME protocol performs much better than the cutoff scheme. In the last case a number of artifacts in the structural organization of the bilayer were observed. All of them were attributed to inadequate treatment of electrostatic interactions of lipid headgroups with counterions. Electrostatic properties, along with structural and dynamic parameters, of both lipid bilayers were investigated. Comparative analysis of the MD data reveals that the water-lipid interface of the DOPC bilayer is looser than that for DOPS. This makes possible deeper penetration of water molecules inside the zwitterionic (DOPC) bilayer, where they strongly interact with carbonyls of lipids. This can lead to thickening of the membrane interface in zwitterionic as compared to negatively charged bilayers.
它们具有流动性且表面带负电荷。了解此类系统中水分子 - 脂质界面的详细分子组织，可能有助于深入了解蛋白质与膜结合的机制。全原子水合脂质双层的分子动力学（MD）是在计算机上解决此问题的最强大工具之一。不幸的是，此类系统计算方法的广泛应用受到严重技术问题的限制。这些问题主要与长程静电效应的正确处理有关。在本研究中，精心构建了1,2 - 二油酰 - sn - 甘油 - 3 - 磷酸丝氨酸（DOPS）阴离子不饱和双层的物理可靠模型，并对其进行了长期MD模拟。静电相互作用采用两种不同算法处理：球形截断函数和粒子网格埃瓦尔德求和（PME）。为了解脂质电荷在系统行为中的作用，还对由1,2 - 二油酰 - sn - 甘油 - 3 - 磷酸胆碱（DOPC）组成的两性离子双层进行了类似计算。结果表明，对于带电荷的DOPS双层，PME协议的性能比截断方案好得多。在后一种情况下，观察到双层结构组织中的许多伪影。所有这些都归因于脂质头部基团与抗衡离子的静电相互作用处理不当。研究了两种脂质双层的静电性质以及结构和动力学参数。MD数据的比较分析表明，DOPC双层的水 - 脂质界面比DOPS双层的更松散。这使得水分子能够更深入地渗透到两性离子（DOPC）双层内部，在那里它们与脂质的羰基强烈相互作用。与带负电荷的双层相比，这可能导致两性离子双层的膜界面增厚。
