Single-molecule protein sequencing through fingerprinting: computational assessment.
Proteins are vital in all biological systems as they constitute the main structural and functional components of cells. Recent advances in mass spectrometry have brought the promise of complete proteomics by helping draft the human proteome. Yet, this commonly used protein sequencing technique has fundamental limitations in sensitivity. Here we propose a method for single-molecule (SM) protein sequencing. A major challenge lies in the fact that proteins are composed of 20 different amino acids, which demands 20 molecular reporters. We computationally demonstrate that it suffices to measure only two types of amino acids to identify proteins and suggest an experimental scheme using SM fluorescence. When achieved, this highly sensitive approach will result in a paradigm shift in proteomics, with major impact in the biological and medical sciences.
Kavli Institute of NanoScience and Department of BioNanoScience, Delft University of Technology, Lorentzweg 1, 2628CJ, Delft, The Netherlands. The Delft Bioinformatics Lab, Department of Intelligent Systems, Delft University of Technology, Mekelweg 4, 2628 CD, Delft, The Netherlands.
Yao
Y
Yao
Margreet
M
Docter
Jetty
J
van Ginkel
Dick
D
de Ridder
Chirlmin
C
Joo
D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D019295:Computational Biology / Q000379:methods; D030562:Databases, Protein; D031541:Fluorescence Resonance Energy Transfer / Q000379:methods; D006801:Humans; D008958:Models, Molecular; D020539:Sequence Analysis, Protein / Q000379:methods*