Pore-peptide Interaction Study of Polycationic-carried Amino Acid for Protein Sequencing

Nanopore sensors could measure electrical signals at the single-molecule level, which possess high sensitivity and selectivity. This characteristic has a broad application prospect in the field of protein sequencing. Biological nanopores have long blockade duration and a high blockade current ratio, which represents higher sensitivity for single molecule detection. However, considering the structural stability and sequencing chip industrialization, solid-state nanopore sequencing may be a long-term development direction in the future, which has been proved in the field of DNA sequencing. Here we simulated the detection of the single amino acid molecule under the traction of a polypeptide cationic carrier, based on silicon nitride nanopores. From the perspective of the potential distribution of nanopores, a more suitable type of traction amino acid was selected. In the steered molecular dynamics, we observed the periodic fluctuation of forces due to atomic scale contact. The specific fluctuation is similar to the fingerprint, which reflects the response of the nanopore to the amino acid. Combining the free energy landscape, differences in energy barriers were observed and provided a reasonable mechanical explanation corresponding to the pore-peptide interaction force. Our results demonstrate the mechanism of single amino acid recognition. These findings may pave the way to solid-state nanopore protein sequencing.