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Lipid composition and salt concentration as regulatory factors of the anion selectivity of VDAC studied by coarse-grained molecular dynamics simulations.
Chemistry and Physics of Lipids ( IF 3.4 ) Pub Date : 2018-11-15 , DOI: 10.1016/j.chemphyslip.2018.11.002 F Van Liefferinge 1 , E-M Krammer 1 , D Sengupta 2 , M Prévost 1
Chemistry and Physics of Lipids ( IF 3.4 ) Pub Date : 2018-11-15 , DOI: 10.1016/j.chemphyslip.2018.11.002 F Van Liefferinge 1 , E-M Krammer 1 , D Sengupta 2 , M Prévost 1
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The voltage-dependent anion channel (VDAC) is a mitochondrial outer membrane protein whose fundamental function is to facilitate and regulate the flow of metabolites between the cytosol and the mitochondrial intermembrane space. Using coarse-grained molecular dynamics simulations, we investigated the dependence of VDAC selectivity towards small inorganic anions on two factors: the ionic strength and the lipid composition. In agreement with experimental data we found that VDAC becomes less anion selective with increasing salt concentration due to the screening of a few basic residues that point into the pore lumen. The molecular dynamics simulations provide insight into the regulation mechanism of VDAC selectivity by the composition in the lipid membrane and suggest that the ion distribution is differently modulated by POPE compared to the POPC bilayer. This occurs through the more persistent interactions of acidic residues located at both rims of the β-barrel with head groups of POPE which in turn impact the electrostatic potential and thereby the selectivity of the pore. This mechanism occurs not only in POPE single component membranes but also in a mixed POPE/POPC bilayer by an enrichment of POPE over POPC lipids on the surface of VDAC. Thus we show here that computationally-inexpensive coarse-grained simulations are able to capture, in a semi-quantitative way, essential features of VDAC anion selectivity and could pave the way toward a molecular level understanding of metabolite transport in natural membranes.
中文翻译：
通过粗粒度分子动力学模拟研究了脂质组成和盐浓度作为VDAC阴离子选择性的调节因素。
电压依赖性阴离子通道（VDAC）是一种线粒体外膜蛋白，其基本功能是促进和调节细胞溶胶与线粒体膜间空间之间代谢产物的流动。使用粗粒度的分子动力学模拟，我们研究了VDAC对小的无机阴离子的选择性对两个因素的依赖性：离子强度和脂质组成。与实验数据一致，我们发现由于筛选了一些指向孔腔的碱性残基，VDAC随盐浓度的增加而变得对阴离子的选择性降低。分子动力学模拟通过脂质膜中的成分提供了对VDAC选择性调节机制的见解，并表明与POPC双层相比，POPE对离子分布的调节不同。这是通过位于β-桶的两个边缘的酸性残基与POPE的头基之间更持久的相互作用而发生的，而这反过来又会影响静电势，进而影响孔的选择性。通过在VDAC表面上的POPC脂质上富集POPE，不仅在POPE单组分膜中，而且在混合的POPE / POPC双层中都发生这种机理。因此，我们在这里表明，计算上便宜的粗粒度模拟能够以半定量方式捕获，
更新日期：2018-11-15
中文翻译：
通过粗粒度分子动力学模拟研究了脂质组成和盐浓度作为VDAC阴离子选择性的调节因素。
电压依赖性阴离子通道（VDAC）是一种线粒体外膜蛋白，其基本功能是促进和调节细胞溶胶与线粒体膜间空间之间代谢产物的流动。使用粗粒度的分子动力学模拟，我们研究了VDAC对小的无机阴离子的选择性对两个因素的依赖性：离子强度和脂质组成。与实验数据一致，我们发现由于筛选了一些指向孔腔的碱性残基，VDAC随盐浓度的增加而变得对阴离子的选择性降低。分子动力学模拟通过脂质膜中的成分提供了对VDAC选择性调节机制的见解，并表明与POPC双层相比，POPE对离子分布的调节不同。这是通过位于β-桶的两个边缘的酸性残基与POPE的头基之间更持久的相互作用而发生的，而这反过来又会影响静电势，进而影响孔的选择性。通过在VDAC表面上的POPC脂质上富集POPE，不仅在POPE单组分膜中，而且在混合的POPE / POPC双层中都发生这种机理。因此，我们在这里表明，计算上便宜的粗粒度模拟能够以半定量方式捕获，
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