Dessaux Delphine, Mathé Jérôme, Ramirez Rosa, Basdevant Nathalie
Université Paris-Saclay, Univ Evry, CNRS, LAMBE UMR8587, Évry-Courcouronnes 91025, France.
J Phys Chem B. 2022 Jun 3. doi: 10.1021/acs.jpcb.2c01028.
In order to understand the physical processes of nanopore experiments at the molecular level, microscopic information from molecular dynamics is greatly needed. Coarse-grained models are a good alternative to classical all-atom models since they allow longer and faster simulations. We performed coarse-grained molecular dynamics of the ionic transport through the α-hemolysin protein nanopore, inserted into a lipid bilayer surrounded by solvent and ions. For this purpose, we used the MARTINI coarse-grained force field and its polarizable water solvent (PW). Moreover, the electric potential difference applied experimentally was mimicked by the application of an electric field to the system. We present, in this study, the results of 1.5 μs long-molecular dynamics simulations of 12 different systems for which different charged amino acids were neutralized, each of them in the presence of nine different electric fields ranging between ±0.04 V/nm (a total of around 100 simulations). We were able to observe several specific features of this pore, current asymmetry and anion selectivity, in agreement with previous studies and experiments, and we identified the charged amino acids responsible for these current behaviors, therefore validating our coarse-grain approach to study ionic transport through nanopores. We also propose a microscopic explanation of these ionic current features using ionic density maps.
为了在分子水平上理解纳米孔实验的物理过程，非常需要来自分子动力学的微观信息。粗粒化模型是经典全原子模型的一个很好的替代方案，因为它们允许进行更长时间和更快的模拟。我们对插入到由溶剂和离子包围的脂质双分子层中的α-溶血素蛋白纳米孔的离子传输进行了粗粒化分子动力学模拟。为此，我们使用了MARTINI粗粒化力场及其可极化水溶剂（PW）。此外，通过对系统施加电场来模拟实验中施加的电势差。在本研究中，我们展示了对12个不同系统进行的1.5微秒长时间分子动力学模拟的结果，这些系统中不同的带电荷氨基酸被中和，每个系统在九个不同电场（范围在±0.04 V/nm之间）存在的情况下进行模拟（总共约100次模拟）。与先前的研究和实验一致，我们能够观察到这个纳米孔的几个特定特征、电流不对称性和阴离子选择性，并且我们确定了导致这些电流行为的带电荷氨基酸，从而验证了我们用于研究通过纳米孔的离子传输的粗粒化方法。我们还使用离子密度图对这些离子电流特征提出了微观解释。
