Single-Molecule Protein Identification by Sub-Nanopore Sensors
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 analyzing the electrical current blockade signal (nanospectrum) resulting from the translocation of a denaturated, linearly charged protein through a sub-nanopore. We further describe the first SMPI algorithm, compute the p-values of Protein-Nanospectrum Matches, and discuss the promise and computational limitations of the current SMPI technology.
