Zhang Dong, Zhang Mingjiao, Zhou Ruhong
Institute of Quantitative Biology, College of Life Sciences, and School of Physics, Zhejiang University, Hangzhou, Zhejiang 310058, China.
J Phys Chem B. 2025 Jan 23;129(3):876-885. doi: 10.1021/acs.jpcb.4c07041. Epub 2025 Jan 13.
The emergence of nanopores in two-dimensional (2D) nanomaterials offers an attractive solid-state platform for high-throughput and low-cost DNA sequencing. However, several challenges remain to be addressed before their wide application, including the too-fast DNA translocation speed (compared to state-of-the-art single nucleoside detection techniques) and too large noise/signal ratios due to DNA fluctuations inside the nanopores. Here, we use molecular dynamics (MD) simulations to demonstrate the feasibility of utilizing RNA-DNA interactions in modulating DNA translocations in 2D MoS nanopores. By constructing a transmembrane-RNA-oligonucleotide-decorated nanopore (TOD nanopore), we find that the translocation speed of DNA can be significantly slowed in a sequence-dependent manner, with up to 160-fold deceleration compared with the naked control. The strong interactions between the translocating DNA and the first and second guanines of transmembrane RNAs are thought to play a key role in regulating the translocation process. Moreover, the observed suppression of base conformational fluctuations within the TOD nanopore can further improve the single nucleotide detecting resolution. Therefore, our investigations demonstrate that the proposed TOD nanopore can be a potential candidate for enhanced DNA sequencing with solid-state nanopores.
二维（2D）纳米材料中纳米孔的出现为高通量、低成本的DNA测序提供了一个有吸引力的固态平台。然而，在其广泛应用之前仍有几个挑战需要解决，包括DNA转位速度过快（与最先进的单核苷检测技术相比）以及由于纳米孔内DNA波动导致的噪声/信号比过大。在这里，我们使用分子动力学（MD）模拟来证明利用RNA-DNA相互作用调节二维MoS纳米孔中DNA转位的可行性。通过构建一个跨膜RNA-寡核苷酸修饰的纳米孔（TOD纳米孔），我们发现DNA的转位速度可以以序列依赖的方式显著减慢，与无修饰对照相比减速高达160倍。转位DNA与跨膜RNA的第一个和第二个鸟嘌呤之间的强相互作用被认为在调节转位过程中起关键作用。此外，在TOD纳米孔内观察到的碱基构象波动的抑制可以进一步提高单核苷酸检测分辨率。因此，我们的研究表明，所提出的TOD纳米孔可能是用于增强固态纳米孔DNA测序的潜在候选者。
