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• W3091843203 abstract "Nanopores have been emerged as a powerful tool for analyzing the structural information and interactional properties of a range of biomolecules. The spatial resolution of nanopore is determined by the diameter and effective thickness of its constriction region, but the presence of vestibule or stem structure in protein-based nanopore could negatively affect the sensitivity of the nanopore when applied for genome sequencing and topological analysis of DNA. Recently, alpha-hederin (Ah) has been reported to form a sub-nanometer scale pore structure in lipid membrane. With the simple structure and extremely small effective thickness, the Ah nanopore was shown to discriminate four different types of nucleotides. However, identification of a certain nucleotide in a strand of DNA, which is essential for genome sequencing, remains challenging. Here, we investigated the resolving capability of Ah nanopore to discriminate few nucleotides in a strand of single-stranded DNA, and the factors determining the sensitivity of Ah nanopore. The Ah nanopore was shown to be able to identify as few as three adenosine nucleotides in a strand of poly cytidine, in which the dwell time of the additional current blockade that represents the adenosine residue was in good agreement with their physical length. We also found that the lateral tension and chain pressure generated around the nanopore were influenced by pore's diameter and played as a dependent variables to determine the geometry of nanopore's constriction as well as the spatial resolution of the Ah nanopore. Alpha hederin (Ah) nanopore was synthesized to discriminate the subtle structural difference of nucleotides in a strand of DNA, which is critical for nanopore-based topological analysis of DNA. The Ah nanopore was shown to have a resolving power of identifying as few as three adenosine nucleotides in a strand of poly cytidine. The geometry of pore's constriction region as well as the effective thickness of nanopore, which determine the spatial resolution of nanopore, were found to be regulated by the diameter of Ah nanopore. • Identification of nucleotides in stranded form is of importance for genome sequencing. • Ah nanopore with small effective thickness was fabricated by molecular self-assembly. • Diameter-dependent lateral tension determines the spatial resolution of Ah nanopore. • Subtle structural difference between purine and pyrimidine could be discriminated. • Ah nanopore could identify the presence of three adenosines in a strand of poly-C." @default.
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• W3091843203 date "2021-01-01" @default.
• W3091843203 modified "2023-10-13" @default.
• W3091843203 title "Topological analysis of single-stranded DNA with an alpha-hederin nanopore" @default.
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• W3091843203 doi "https://doi.org/10.1016/j.bios.2020.112711" @default.
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