Abstract

The human proteome has millions of protein variants due to alternative RNA splicing and post-translational modifications, and variants that are related to diseases are frequently present in minute concentrations. For DNA and RNA, low concentrations can be amplified using the polymerase chain reaction, but there is no such reaction for proteins. Therefore, the development of single-molecule protein sequencing is a critical step in the search for protein biomarkers. Here, we show that single amino acids can be identified by trapping the molecules between two electrodes that are coated with a layer of recognition molecules, then measuring the electron tunnelling current across the junction. A given molecule can bind in more than one way in the junction, and we therefore use a machine-learning algorithm to distinguish between the sets of electronic a €fingerprintsa € associated with each binding motif. With this recognition tunnelling technique, we are able to identify D and L enantiomers, a methylated amino acid, isobaric isomers and short peptides. The results suggest that direct electronic sequencing of single proteins could be possible by sequentially measuring the products of processive exopeptidase digestion, or by using a molecular motor to pull proteins through a tunnel junction integrated with a nanopore.

Original languageEnglish (US)
Pages (from-to)466-473
Number of pages8
JournalNature Nanotechnology
Volume9
Issue number6
DOIs
StatePublished - 2014

Fingerprint

Peptides
peptides
amino acids
Amino acids
Spectroscopy
proteins
Proteins
Amino Acids
Molecules
spectroscopy
molecules
sequencing
RNA
Exopeptidases
proteome
polymerase chain reaction
splicing
machine learning
Electron tunneling
Nanopores

ASJC Scopus subject areas

  • Bioengineering
  • Biomedical Engineering
  • Materials Science(all)
  • Electrical and Electronic Engineering
  • Condensed Matter Physics
  • Atomic and Molecular Physics, and Optics

Cite this

Single-molecule spectroscopy of amino acids and peptides by recognition tunnelling. / Zhao, Yanan; Ashcroft, Brian; Zhang, Peiming; Liu, Hao; Sen, Suman; Song, Weisi; Im, Jongone; Gyarfas, Brett; Manna, Saikat; Biswas, Sovan; Borges, Chad; Lindsay, Stuart.

In: Nature Nanotechnology, Vol. 9, No. 6, 2014, p. 466-473.

Research output: Contribution to journalArticle

Zhao, Y, Ashcroft, B, Zhang, P, Liu, H, Sen, S, Song, W, Im, J, Gyarfas, B, Manna, S, Biswas, S, Borges, C & Lindsay, S 2014, 'Single-molecule spectroscopy of amino acids and peptides by recognition tunnelling', Nature Nanotechnology, vol. 9, no. 6, pp. 466-473. https://doi.org/10.1038/nnano.2014.54
Zhao, Yanan ; Ashcroft, Brian ; Zhang, Peiming ; Liu, Hao ; Sen, Suman ; Song, Weisi ; Im, Jongone ; Gyarfas, Brett ; Manna, Saikat ; Biswas, Sovan ; Borges, Chad ; Lindsay, Stuart. / Single-molecule spectroscopy of amino acids and peptides by recognition tunnelling. In: Nature Nanotechnology. 2014 ; Vol. 9, No. 6. pp. 466-473.
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AU - Im, Jongone

AU - Gyarfas, Brett

AU - Manna, Saikat

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AU - Lindsay, Stuart

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