Papers › Single-Molecule Protein Identification by Sub-Nanopore Sensors

Single-Molecule Protein Identification by Sub-Nanopore Sensors

8 Apr 2016arXiv:1604.02270archive 2025-07-28

Mikhail Kolmogorov, Eamonn Kennedy, Zhuxin Dong, Gregory Timp, Pavel Pevzner

Recent advances in top-down mass spectrometry enabled identification of intact proteins, but this technology still faces challenges. For example, top-down mass spectrometry suffers from a lack of sensitivity since the ion counts for a single fragmentation event are often low. In contrast, nanopore technology is exquisitely sensitive to single intact molecules, but it has only been successfully applied to DNA sequencing, so far. Here, we explore the potential of sub-nanopores for single-molecule protein identification (SMPI) and describe an algorithm for identification of the electrical current blockade signal (nanospectrum) resulting from the translocation of a denaturated, linearly charged protein through a sub-nanopore. The analysis of identification p-values suggests that the current technology is already sufficient for matching nanospectra against small protein databases, e.g., protein identification in bacterial proteomes.

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