Sequence-Dependent Slowdown of DNA Translocation Using Transmembrane RNA–DNA Interactions in MoS2 Nanopore

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 MoS₂ 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.