Institute of Quantitative Biology, Department of Physics, and College of Life Sciences, Zhejiang University, 310027 Hangzhou, China.
Laboratory of Experimental Physical Biology, Department of Chemistry, Zhejiang University, 310027 Hangzhou, China.
ACS Appl Mater Interfaces. 2022 Jul 20;14(28):32618-32624. doi: 10.1021/acsami.2c03335. Epub 2022 Jul 7.
Nanopores in two-dimensional (2D) materials have emerged to offer in principle necessary spatial resolution for high-throughput DNA sequencing. However, their fidelity is severely limited by the fast DNA translocation. A recent experiment indicates that introducing ionic liquids could slow down DNA translocation in a MoS nanopore. However, the corresponding in-depth molecular mechanism underlying the experimental findings is not fully understood, which is crucial for the future improvement of rational DNA translocation control. Here, we computationally investigate and then experimentally identify the effect of BmimCl ionic liquid on the retardation of ssDNA translocation through a single-layer MoS nanopore. Our all-atom molecular dynamics simulations demonstrate that the strong interaction between Bmim and ssDNA offers a considerable dragging force to decelerate the electrophoretic motion of ssDNA in the BmimCl solution. Moreover, we show that Bmim ions exhibit preferential binding on the sulfur edges of the nanopore. These Bmim in the pore region can not only act as a steric blockage but also form π-π stackings with nucleobases, which provide a further restriction on the ssDNA motion. Therefore, our molecular dynamics simulation investigations deepen the understanding of the critical role of ionic liquid in DNA translocation through a nanopore from a molecular landscape, which may benefit practical implementations of ionic liquids in nanopore sequencing.
二维（2D）材料中的纳米孔在理论上为高通量 DNA 测序提供了必要的空间分辨率。然而，它们的准确性受到快速 DNA 迁移的严重限制。最近的一项实验表明，在 MoS 纳米孔中引入离子液体可以减缓 DNA 的迁移。然而，对于实验结果背后的相应深入分子机制还不完全了解，这对于未来合理控制 DNA 迁移的改进至关重要。在这里，我们通过计算研究并随后通过实验确定了 BmimCl 离子液体对单层 MoS 纳米孔中单链 DNA 迁移的延迟作用。我们的全原子分子动力学模拟表明，Bmim 与 ssDNA 之间的强相互作用提供了相当大的拖曳力，以减缓 BmimCl 溶液中 ssDNA 的电泳运动。此外，我们表明 Bmim 离子优先结合在纳米孔的硫边缘上。这些孔区中的 Bmim 不仅可以作为空间位阻，还可以与碱基形成π-π 堆积，从而进一步限制 ssDNA 的运动。因此，我们的分子动力学模拟研究从分子水平加深了对离子液体在纳米孔 DNA 迁移中关键作用的理解，这可能有利于离子液体在纳米孔测序中的实际应用。
