Farshad Mohsen, Rasaiah Jayendran C
Department of Chemistry, University of Maine, Orono, Maine 04469, United States.
J Phys Chem B. 2021 Mar 25;125(11):2863-2870. doi: 10.1021/acs.jpcb.0c10759. Epub 2021 Mar 10.
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 A, G, T, and C 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.
通过多个CsgG纳米孔对离子电流进行多次并行读取，可提供有关离子-核苷酸相互作用的信息，以便使用碱基识别算法对单链DNA（ss-DNA）进行测序。然而，离子-核苷酸相互作用中的信息对于单读纳米孔DNA测序似乎并不充分。在此，我们报告了根据密度泛函理论（DFT）计算出的有区别的光-核苷酸相互作用，并将其与从分子动力学（MD）模拟获得的离子电流进行比较。MD模拟是在一个包含横向纳米通道和纵向固态纳米孔的系统上进行的。我们表明，A、G、T和C通过纳米孔转运过程中的横向和纵向离子电流广泛重叠。另一方面，不同类型的单核苷酸、核苷和核碱基的紫外-可见光谱和拉曼光谱显示出比离子电流相对更高的分辨率。与用于纳米孔DNA测序的离子-核苷酸相互作用相比，光-核苷酸相互作用为表征核苷酸提供了更好的信息。这可以通过使用包括表面增强拉曼光谱（SERS）或尖端增强拉曼光谱（TERS）在内的光学技术来实现，同时等离子体激发可用于定位光并控制核苷酸流动速率。
