tRNA Modification Detection Using Graphene Nanopores: A Simulation Study

Authors

Thomas J. Begley, University at Albany, State University of New York
Khadijiah Onanuga, University at Albany, State University of New York
Alan A. Chen, University at Albany, State University of New York
Srivathsan V. Ranganathan, University at Albany, State University of New York

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Document Type

Article

Publication Date

8-25-2017

DOI

https://doi.org/10.3390/biom7030065

Abstract

There are over 100 enzyme-catalyzed modifications on transfer RNA (tRNA) molecules. The levels and identity of wobble uridine (U) modifications are affected by environmental conditions and diseased states, making wobble U detection a potential biomarker for exposures and pathological conditions. The current detection of RNA modifications requires working with nucleosides in bulk samples. Nanopore detection technology uses a single-molecule approach that has the potential to detect tRNA modifications. To evaluate the feasibility of this approach, we have performed all-atom molecular dynamics (MD) simulation studies of a five-layered graphene nanopore by localizing canonical and modified uridine nucleosides. We found that in a 1 M KCl solution with applied positive and negative biases not exceeding 2 V, nanopores can distinguish U from 5-carbonylmethyluridine (cm⁵U), 5-methoxycarbonylmethyluridine (mcm⁵U), 5-methoxycarbonylmethyl-2-thiouridine (mcm⁵s²U), and 5-methoxycarbonylmethyl-2′-O-methyluridine (mcm⁵Um) based on changes in the resistance of the nanopore. Specifically, we observed that in nanopores with dimensions less than 3 nm diameter, a localized mcm⁵Um and mcm⁵U modifications could be clearly distinguished from the canonical uridine, while the other modifications showed a modest yet detectable decrease in their respective nanopore conductance. We have compared the results between nanopores of various sizes to aid in the design, optimization, and fabrication of graphene nanopores devices for tRNA modification detection.

Comments

This is the Publisher’s PDF of the following article made available by Biomolecules: Onanuga K, Begley TJ, Chen AA, Ranganathan SV. tRNA Modification Detection Using Graphene Nanopores: A Simulation Study. Biomolecules. 2017; 7(3):65. https://doi.org/10.3390/biom7030065

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

Begley, Thomas J.; Onanuga, Khadijiah; Chen, Alan A.; and Ranganathan, Srivathsan V., "tRNA Modification Detection Using Graphene Nanopores: A Simulation Study" (2017). Biological Sciences Faculty Scholarship. 34.
https://scholarsarchive.library.albany.edu/biology_fac_scholar/34