Slowing Down Peptide Translocation through MoSi₂N₄ Nanopores for Protein Sequencing

Precise identification and quantification of amino acids are crucial for numerous biological applications. A significant challenge in the development of high-throughput, cost-effective nanopore protein sequencing technology is the rapid translocation of protein through the nanopore, which hinders accurate sequencing. In this study, we explore the potential of nanopore constructed from a novel two-dimensional (2D) material MoSi₂N₄ in decelerating the velocity of protein translocation using molecular dynamics simulations. The translocation velocity of the peptide through the MoSi₂N₄ nanopore can be reduced by nearly an order of magnitude compared to the MoS₂ nanopore. Systematic analysis reveals that this reduction is due to stronger interaction between the peptide and MoSi₂N₄ membrane surface, particularly for aromatic residues, as they contain aromatic rings composed of relatively nonpolar C-C and C-H bonds. By adjusting the proportion of aromatic residues in peptides, further control over peptide translocation velocity can be achieved. Additionally, the system validates the feasibility of using an appropriate nanopore diameter for protein sequencing. The theoretical investigations presented herein suggest a potential method for manipulating protein translocation kinetics, promising more effective and economical advancements in nanopore protein sequencing technology.