Discrimination of Single and Isomeric Amino Acids in Peptides Using a Multi-Walled Carbon Nanotube Porin Sensing System

Abstract

Precise amino acid identification is critical for many biological applications but remains limited by the lack of methods to resolve subtle differences between proteinogenic residues and their substitutions. Here, we present a multi-walled carbon nanotube porin sensing system to identify single and isomeric amino acids in peptides. Molecular dynamics simulations reveal that strong van der Waals (vdW) interactions between peptide side chains and the nanotube interior slow translocation, with the interaction strength varying by amino acid. By utilizing the smooth tubular structure of the carbon nanotube’s inner wall, we demonstrate the ability to simultaneously consider steric hindrance effects and vdW interactions as the primary factors for distinguishing proteinogenic amino acids. We show that the sensing system can directly identify up to 10 proteinogenic amino acids, including isomers, and locate single-residue substitutions in peptides at subnanometer resolution. These findings have the potential to lay the foundation for protein sequencing.