Kinetic proofreading can enhance specificity in a non-enzymatic DNA strand displacement network
Author(s)
Mukherjee, Rakesh
Sengar, Aditya
Cabello Garcia, Javier
Ouldridge, Thomas
Type
Journal Article
Abstract
Kinetic proofreading is used throughout natural systems to enhance the specificity of molecular recognition. At its
most basic level, kinetic proofreading uses a supply of chemical fuel to drive a recognition interaction out of equilibrium, allowing
a single free-energy difference between correct and incorrect targets to be exploited two or more times. Despite its importance in
biology, there has been little effort to incorporate kinetic proofreading into synthetic systems in which molecular recognition is
important, such as nucleic acid nanotechnology. In this article, we introduce a DNA strand displacement-based kinetic proofreading
motif, showing that the consumption of a DNA-based fuel can be used to enhance molecular recognition during a templated dimeri zation reaction. We then show that kinetic proofreading can enhance the specificity with which a probe discriminates single nucleo tide mutations, both in terms of the initial rate with which the probe reacts and the long-time behaviour.
most basic level, kinetic proofreading uses a supply of chemical fuel to drive a recognition interaction out of equilibrium, allowing
a single free-energy difference between correct and incorrect targets to be exploited two or more times. Despite its importance in
biology, there has been little effort to incorporate kinetic proofreading into synthetic systems in which molecular recognition is
important, such as nucleic acid nanotechnology. In this article, we introduce a DNA strand displacement-based kinetic proofreading
motif, showing that the consumption of a DNA-based fuel can be used to enhance molecular recognition during a templated dimeri zation reaction. We then show that kinetic proofreading can enhance the specificity with which a probe discriminates single nucleo tide mutations, both in terms of the initial rate with which the probe reacts and the long-time behaviour.
Date Issued
2024-07-17
Date Acceptance
2024-06-14
Citation
Journal of the American Chemical Society, 2024, 146 (28), pp.18916-18926
ISSN
0002-7863
Publisher
American Chemical Society
Start Page
18916
End Page
18926
Journal / Book Title
Journal of the American Chemical Society
Volume
146
Issue
28
Copyright Statement
Copyright © 2024 The Authors. Published by American Chemical Society. This publication is licensed under
CC-BY 4.0.
License
CC-BY 4.0.
License
License URL
Identifier
https://pubs.acs.org/doi/10.1021/jacs.3c14673
Publication Status
Published
Date Publish Online
2024-07-01