DNA hairpins destabilize duplexes primarily by promoting melting rather than by inhibiting hybridization

John S. Schreck, Thomas E. Ouldridge, Flavio Romano, Petr Sulc, Liam P. Shaw, Ard A. Louis, Jonathan P K Doye

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

The effect of secondary structure on DNA duplex formation is poorly understood. Using oxDNA, a nucleotide level coarse-grained model of DNA, we study how hairpins influence the rate and reaction pathways of DNA hybridzation. We compare to experimental systems studied by Gao et al. (1) and find that 3-base pair hairpins reduce the hybridization rate by a factor of 2, and 4-base pair hairpins by a factor of 10, compared to DNA with limited secondary structure, which is in good agreement with experiments. By contrast, melting rates are accelerated by factors of ∼100 and ∼2000. This surprisingly large speed-up occurs because hairpins form during the melting process, and significantly lower the free energy barrier for dissociation. These results should assist experimentalists in designing sequences to be used in DNA nanotechnology, by putting limits on the suppression of hybridization reaction rates through the use of hairpins and offering the possibility of deliberately increasing dissociation rates by incorporating hairpins into single strands.

Original languageEnglish (US)
Pages (from-to)6181-6190
Number of pages10
JournalNucleic Acids Research
Volume43
Issue number13
DOIs
StatePublished - May 22 2015
Externally publishedYes

Fingerprint

Freezing
DNA
Base Pairing
Nanotechnology
Nucleotides

ASJC Scopus subject areas

  • Genetics
  • Medicine(all)

Cite this

Schreck, J. S., Ouldridge, T. E., Romano, F., Sulc, P., Shaw, L. P., Louis, A. A., & Doye, J. P. K. (2015). DNA hairpins destabilize duplexes primarily by promoting melting rather than by inhibiting hybridization. Nucleic Acids Research, 43(13), 6181-6190. https://doi.org/10.1093/nar/gkv582

DNA hairpins destabilize duplexes primarily by promoting melting rather than by inhibiting hybridization. / Schreck, John S.; Ouldridge, Thomas E.; Romano, Flavio; Sulc, Petr; Shaw, Liam P.; Louis, Ard A.; Doye, Jonathan P K.

In: Nucleic Acids Research, Vol. 43, No. 13, 22.05.2015, p. 6181-6190.

Research output: Contribution to journalArticle

Schreck, JS, Ouldridge, TE, Romano, F, Sulc, P, Shaw, LP, Louis, AA & Doye, JPK 2015, 'DNA hairpins destabilize duplexes primarily by promoting melting rather than by inhibiting hybridization', Nucleic Acids Research, vol. 43, no. 13, pp. 6181-6190. https://doi.org/10.1093/nar/gkv582
Schreck, John S. ; Ouldridge, Thomas E. ; Romano, Flavio ; Sulc, Petr ; Shaw, Liam P. ; Louis, Ard A. ; Doye, Jonathan P K. / DNA hairpins destabilize duplexes primarily by promoting melting rather than by inhibiting hybridization. In: Nucleic Acids Research. 2015 ; Vol. 43, No. 13. pp. 6181-6190.
@article{df5b4c61fd894d938611ae94b6be2495,
title = "DNA hairpins destabilize duplexes primarily by promoting melting rather than by inhibiting hybridization",
abstract = "The effect of secondary structure on DNA duplex formation is poorly understood. Using oxDNA, a nucleotide level coarse-grained model of DNA, we study how hairpins influence the rate and reaction pathways of DNA hybridzation. We compare to experimental systems studied by Gao et al. (1) and find that 3-base pair hairpins reduce the hybridization rate by a factor of 2, and 4-base pair hairpins by a factor of 10, compared to DNA with limited secondary structure, which is in good agreement with experiments. By contrast, melting rates are accelerated by factors of ∼100 and ∼2000. This surprisingly large speed-up occurs because hairpins form during the melting process, and significantly lower the free energy barrier for dissociation. These results should assist experimentalists in designing sequences to be used in DNA nanotechnology, by putting limits on the suppression of hybridization reaction rates through the use of hairpins and offering the possibility of deliberately increasing dissociation rates by incorporating hairpins into single strands.",
author = "Schreck, {John S.} and Ouldridge, {Thomas E.} and Flavio Romano and Petr Sulc and Shaw, {Liam P.} and Louis, {Ard A.} and Doye, {Jonathan P K}",
year = "2015",
month = "5",
day = "22",
doi = "10.1093/nar/gkv582",
language = "English (US)",
volume = "43",
pages = "6181--6190",
journal = "Nucleic Acids Research",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "13",

}

TY - JOUR

T1 - DNA hairpins destabilize duplexes primarily by promoting melting rather than by inhibiting hybridization

AU - Schreck, John S.

AU - Ouldridge, Thomas E.

AU - Romano, Flavio

AU - Sulc, Petr

AU - Shaw, Liam P.

AU - Louis, Ard A.

AU - Doye, Jonathan P K

PY - 2015/5/22

Y1 - 2015/5/22

N2 - The effect of secondary structure on DNA duplex formation is poorly understood. Using oxDNA, a nucleotide level coarse-grained model of DNA, we study how hairpins influence the rate and reaction pathways of DNA hybridzation. We compare to experimental systems studied by Gao et al. (1) and find that 3-base pair hairpins reduce the hybridization rate by a factor of 2, and 4-base pair hairpins by a factor of 10, compared to DNA with limited secondary structure, which is in good agreement with experiments. By contrast, melting rates are accelerated by factors of ∼100 and ∼2000. This surprisingly large speed-up occurs because hairpins form during the melting process, and significantly lower the free energy barrier for dissociation. These results should assist experimentalists in designing sequences to be used in DNA nanotechnology, by putting limits on the suppression of hybridization reaction rates through the use of hairpins and offering the possibility of deliberately increasing dissociation rates by incorporating hairpins into single strands.

AB - The effect of secondary structure on DNA duplex formation is poorly understood. Using oxDNA, a nucleotide level coarse-grained model of DNA, we study how hairpins influence the rate and reaction pathways of DNA hybridzation. We compare to experimental systems studied by Gao et al. (1) and find that 3-base pair hairpins reduce the hybridization rate by a factor of 2, and 4-base pair hairpins by a factor of 10, compared to DNA with limited secondary structure, which is in good agreement with experiments. By contrast, melting rates are accelerated by factors of ∼100 and ∼2000. This surprisingly large speed-up occurs because hairpins form during the melting process, and significantly lower the free energy barrier for dissociation. These results should assist experimentalists in designing sequences to be used in DNA nanotechnology, by putting limits on the suppression of hybridization reaction rates through the use of hairpins and offering the possibility of deliberately increasing dissociation rates by incorporating hairpins into single strands.

UR - http://www.scopus.com/inward/record.url?scp=84939632443&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84939632443&partnerID=8YFLogxK

U2 - 10.1093/nar/gkv582

DO - 10.1093/nar/gkv582

M3 - Article

VL - 43

SP - 6181

EP - 6190

JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

IS - 13

ER -