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Computational design of probes to detect bacterial genomes by multivalent binding
File(s)
1918274117.full.pdf (1.1 MB)
Published version
OA Location
Author(s)
Curk, Tine
Brackley, Chris A
Farrell, James D
Xing, Zhongyang
Joshi, Darshana
Type
Journal Article
Abstract
Rapid methods for diagnosis of bacterial infections are urgently needed to reduce inappropriate use of antibiotics, which contributes to antimicrobial resistance. In many rapid diagnostic methods, DNA oligonucleotide probes, attached to a surface, bind to specific nucleotide sequences in the DNA of a target pathogen. Typically, each probe binds to a single target sequence; i.e., target-probe binding is monovalent. Here we show using computer simulations that the detection sensitivity and specificity can be improved by designing probes that bind multivalently to the entire length of the pathogen genomic DNA, such that a given probe binds to multiple sites along the target DNA. Our results suggest that multivalent targeting of long pieces of genomic DNA can allow highly sensitive and selective binding of the target DNA, even if competing DNA in the sample also contains binding sites for the same probe sequences. Our results are robust to mild fragmentation of the bacterial genome. Our conclusions may also be relevant for DNA detection in other fields, such as disease diagnostics more broadly, environmental management, and food safety.
Date Issued
2020-04-21
Date Acceptance
2020-03-28
Citation
Proceedings of the National Academy of Sciences of USA, 2020, 117 (17), pp.8719-8726
URI
URL
DOI
ISSN
0027-8424
Publisher
National Academy of Sciences
Start Page
8719
End Page
8726
Journal / Book Title
Proceedings of the National Academy of Sciences of USA
Volume
117
Issue
17
Copyright Statement
© 2020 the Author(s). Published by PNAS.
This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/).
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/32241887
PII: 1918274117
Subjects
DNA-based detection
computer simulations
multivalent binding
polymer physics
superselectivity
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2020-04-02