Abstract:
The single molecule measurement has enhanced the precision and depth of our knowledge about living system. Learning from nature, the million years of evolution have produced the membrane proteins which acts as a single biomolecule interface for capturing and identifying a single molecule of interests, and makes biological process occurring. Here, we focus on the biological nanopore-based single biomolecule interface for single molecule measurements.1-3 We outline the design of nanopore-based single biomolecule interface which provides rich heterogeneities and stochastics information about each molecule. Then, we focus on the future areas beyond DNA sequencing including detecting rare species, resolving the hidden intermediates, depicting the spectra for the covalent/non-covalent interactions, tracing the dynamic pathways of single molecule behaviors.4-5 A concept “single-molecule ionic spectrum”, which is considered as “a special music of molecule”, may potentially map the non-covalent interaction at atomic level in future. Since the characteristic interaction determines the sensitivity of nanopore, ideally the frequency analysis of nanopore data could be used not only for DNA sequencing, RNA sequencing, protein sequencing but also all kinds of single molecule detection. As ideally transferring the frequency-energy spectrum from the ionic current into the voice frequency, we illustrate that a nanopore-based single-biomolecule interface likes a tuba. When a single analyte flows into the ‘tuba’, its dynamic interaction with the pore could be modulated by the residue of the pore (‘button’) and the resonance space at the single-molecule interface (‘tuba’). As a result, the beautiful music of a single molecule will be played with a typical rhythm and melody.
A self-assembled aerolysin membrane protein exampled as single biomolecule interface. The oligonucleotide is taken as an example for illustrating the analyte. Single-molecule music. Ideally, transferring the frequency-energy spectrum from the ionic current into the voice frequency could possibly let us hear produce the rhythm from membrane channels. A single-biomolecule interface derived from a single recognition molecule at the nano-interface.
REFERENCES
1. Y.-L. Ying, C. Chao, Y.-X. Hu. Y.-T. Long, A single biomolecule interface for advancing the sensitivity, selectivity, and accuracy of sensors, Natl. Sci. Rev., 2018, 450-520.
2. Y.-Q. Wang, C. Cao, Y.-L. Ying, S. Li, M.-B. Wang, J. Huang, Y.-T. Long, Rationally Designed Sensing Selectivity and Sensitivity of an Aerolysin Nanopore via Site-Directed Mutagenesis, ACS Sens., 2018, 779-783.
3. Y.-Q. Wang, M.-Y. Li, H. Qiu, C. Cao, M.-B. Wang, X.-Y. Wu, J. Huang, Y.-L. Ying, Y.-T. Long, Identification of Essential Sensitive Regions of the Aerolysin Nanopore for Single Oligonucleotide Analysis, Anal. Chem., 2018, 7790-7794.
4. C. Cao, Y.-L. Ying, Z.-L. Hu, D.-F. Liao, H. Tian, Y.-T. Long*. Discrimination of oligonucleotides of different length with a wild-type aerolysin nanopore. Nat. Nanotechnol., 2016, 11, 713-716.
5. C. Cao, M.-Y. Li, N. Cirauqui, Y.-Q. Wang, M. D. Peraro, H. Tian, Y.-T. Long. Mapping the sensing spots of aerolysin for single oligonucleotides analysis, Nat. Commun., 2018, 2823-2830.
Biography:
Yi-Tao Long, B.Sc. (1989) in Chemistry at Shandong University, M.Sc. (1996) and Ph.D. (1998) in Bioelectrochemistry from Nanjing University. postdoctoral study at Heidelberg University (1999-2001), research associate at University of Saskatchewan and University of Alberta (2001-2006). senior research scientist at UC Berkeley (2006-2007). professor at East China University of Science and Technology (2007-2018). Professor at State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University (2019-). Associate Editor for Chemical Science. His research focuses on nanopore confined single molecule analysis, in-situ nanospectroelectrochemistry, intelligent biosensors and bio-interphase.
Prof. Yi-Tao Long, is a Changjiang Scholar in China, and he’s also the associate editor of multiple journals including Chemical Science. His research interests include Single-Molecule Interface, Electrochemically Nanoconfined Space, Nanopore Single Molecule Analysis, Nanoelectrochemistry, in-situ Spectroelectrochemistry.