Nanopore Stochastic Sensing Based on Non-covalent Interactions

Abstract

A variety of species could be detected by using nanopores engineered with various recognition sites based upon non-covalent interactions, including electrostatic, aromatic, and hydrophobic interactions. The existence of these engineered non-covalent bonding sites was supported by the single-channel recording technique. The advantage of the non-covalent interaction-based sensing strategy was that the recognition site of the engineered nanopore was not specific for a particular molecule but instead selective for a class of species (e.g., cationic, anionic, aromatic, and hydrophobic). Since different species produce current modulations with quite different signatures represented by amplitude, residence time, and even characteristic voltage-dependence curve, the non-covalent interaction-based nanopore sensor could not only differentiate individual molecules in the same category but also enable differentiation between species with similar structures or molecular weights. Hence, our developed non-covalent interaction-based nanopore sensing strategy may find useful application in the detection of molecules of medical and/or environmental importance.

An engineered third electrostatic constriction of aerolysin to manipulate heterogeneously charged peptide transport

“…Even so, various types of biological nanopores have been engineered for studying peptide translocation, analysing peptide interactions and controlling single protein/peptide capture and translocation through non-covalent interactions. 10–15 Wild-type aerolysin (WT AeL) has shown an excellent ability to discriminate amino acids from short peptides with the help of a charged polyarginine carrier, which holds promise for peptide sequencing. But WT AeL hardly provides effective ionic current responses to all heterogeneously charged peptides.…”

Identification of Single Amino Acid Chiral and Positional Isomers Using an Electrostatically Asymmetric Nanopore

“…Protein nanopores have already been utilized to identify single amino acids − and protein–protein interactions by amperometric recognition. Peptides with post-translational modifications are recognized by nanopore-based approaches, to the extent that the sensing principle relies on volume exclusion. , Moreover, the inter-molecule interaction between the target peptides and the nanopore interface can lead to characteristic ionic current patterns for discriminating amino acids with similar volumes. , The nanopore-based single molecule approach has demonstrated the possibility of sensing chiral molecules by designing a specific chiral environment, but the generalization of such a strategy toward peptide-containing chiral amino acid is lacking. − Previous nanopore-based tools remain insufficient in identifying amino acids in peptides with identical volumes.…”

A molecular dynamics investigation of Taq DNA polymerase and its complex with a DNA substrate using a solid-state nanopore biosensor

“…electrostatic, aromatic, and hydrophobic interactions) in the α-HL nanopore, Chen et al can detect various molecules based on their ionic current signal. 47 Therefore, based on previous studies, we tried to use MD simulation in a microscopic view to explore the correlation between non-covalent interaction and ionic current blockage.…”