Light-Nucleotide versus Ion-Nucleotide Interactions for Single-Nucleotide Resolution

Several parallel reads of ionic currents through multiple CsgG nanopores provide information about ion-nucleotide interactions for sequencing single-stranded DNA (ss-DNA) using base-calling algorithms. However, the information in ion-nucleotide interactions seems insufficient for single-read nanopore DNA sequencing. Here we report discriminative light-nucleotide interactions calculated from density functional theory (DFT), which are compared with ionic currents obtained from molecular dynamics (MD) simulations. The MD simulations were performed on a system containing a transverse nanochannel and a longitudinal solid state nanopore. We show that both of the transverse and longitudinal ionic currents during the translocation of A₁₆, G₁₆, T₁₆, and C₁₆ through the nanopore, overlapped widely. On the other hand, the UV-vis and Raman spectra of different types of single nucleotides, nucleosides, and nucleobases show relatively higher resolution than the ionic currents. Light-nucleotide interactions provide better information for characterizing the nucleotides in comparison to ion-nucleotide interactions for nanopore DNA sequencing. This can be realized by using optical techniques including surface-enhanced Raman spectroscopy (SERS) or tip-enhanced Raman spectroscopy (TERS), while plasmon excitation can be used to localize light and control the rate of nucleotide flow.