Toward single-molecule protein sequencing using nanopores

Over the past three decades, biological nanopore sequencing has grown from a research curiosity to a mature technology to sequence nucleic acids at the single-molecule level. Now, recent achievements suggest that nanopores might be able to sequence proteins soon. In this Perspective, we analyze the different approaches that have been proposed to measure proteins and peptides using nanopores. We predict that, more likely than not, nanopores will be capable of identifying full-length proteins at the single-molecule level and with single-amino acid resolution, paving the way to single-molecule protein sequencing. This would allow several applications in proteomics that are at present challenging, including measuring the heterogeneity of post-translational modifications, quantifying low-abundance proteins and characterizing protein splicing.