Distinguishing between Similar Miniproteins with Single-Molecule Nanopore Sensing: A Computational Study.
| Autor: | Cardoch S; Department of Physics and Astronomy, Uppsala University, Box 516, SE-751 20 Uppsala, Sweden., Timneanu N; Department of Physics and Astronomy, Uppsala University, Box 516, SE-751 20 Uppsala, Sweden., Caleman C; Center for Free-Electron Laser Science, Deutsches Elektronen-Synchrotron DESY, Notkestraße 85, 22607 Hamburg, Germany.; Department of Physics and Astronomy, Uppsala University, Box 516, SE-751 20 Uppsala, Sweden., Scheicher RH; Department of Physics and Astronomy, Uppsala University, Box 516, SE-751 20 Uppsala, Sweden. |
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| Jazyk: | angličtina |
| Zdroj: | ACS nanoscience Au [ACS Nanosci Au] 2021 Dec 28; Vol. 2 (2), pp. 119-127. Date of Electronic Publication: 2021 Dec 28 (Print Publication: 2022). |
| DOI: | 10.1021/acsnanoscienceau.1c00022 |
| Abstrakt: | A nanopore is a tool in single-molecule sensing biotechnology that offers label-free identification with high throughput. Nanopores have been successfully applied to sequence DNA and show potential in the study of proteins. Nevertheless, the task remains challenging due to the large variability in size, charges, and folds of proteins. Miniproteins have a small number of residues, limited secondary structure, and stable tertiary structure, which can offer a systematic way to reduce complexity. In this computational work, we theoretically evaluated sensing two miniproteins found in the human body using a silicon nitride nanopore. We employed molecular dynamics methods to compute occupied-pore ionic current magnitudes and electronic structure calculations to obtain interaction strengths between pore wall and miniprotein. From the interaction strength, we derived dwell times using a mix of combinatorics and numerical solutions. This latter approach circumvents typical computational demands needed to simulate translocation events using molecular dynamics. We focused on two miniproteins potentially difficult to distinguish owing to their isotropic geometry, similar number of residues, and overall comparable structure. We found that the occupied-pore current magnitudes not to vary significantly, but their dwell times differ by 1 order of magnitude. Together, these results suggest a successful identification protocol for similar miniproteins. Competing Interests: The authors declare no competing financial interest. (© 2021 The Authors. Published by American Chemical Society.) |
| Databáze: | MEDLINE |
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