Unveiling the Microscopic Mechanism of Current Variation in the Sensing Region of the MspA Nanopore for DNA Sequencing
- 15 September 2021
- journal article
- research article
- Published by American Chemical Society (ACS) in The Journal of Physical Chemistry Letters
- Vol. 12 (37), 9132-9141
- https://doi.org/10.1021/acs.jpclett.1c02414
Abstract
Different nucleotides generate specific ionic currents that discriminate between the nucleotides while they are passing through the nanopore constriction. MspA is a commonly used nanopore for DNA sequencing. However, the reasons of the current variation remain ambiguous. Our work unveils the microscopic mechanism of current variation for an ssDNA passing through the MspA nanopore by all-atom molecular dynamic simulations. Besides the physical rigidity and dimensions of the nucleotides, nucleotide orientation is observed to induce nonignorable current variation. Besides the generally considered MspA nanopore constriction, it is also found that the region below constriction could be used to detect and differentiate single nucleotides when the single-stranded DNA translocates in the form of base–constriction–base meshing and ratcheting across the nanopore constriction compared to other regions. The work provides a novel insight into facilitating the development of low-cost and high-throughput nanopore DNA sequencing.Funding Information
- Natural Science Foundation of Jiangsu Province (BK20190358)
- National Natural Science Foundation of China (21804092, 51905097, 52075099)
- Southeast University
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