Effect of loop distortion on the stability and structural dynamics of DNA hairpin and dumbbell conjugates

Martin McCullagh, Ligang Zhang, Andrew H. Karaba, Huihe Zhu, George C Schatz, Frederick D. Lewis

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

The thermal stability and conformational dynamics of DNA hairpin and dumbbell conjugates having short A-tract base pair domains connected by tri- or hexa(ethylene glycol) linkers is reported. The formation of stable base-paired A-tract hairpins having oligo(ethylene glycol) linkers requires a minimum of four or five A-T base pairs. The formation of base-paired dumbbells having oligo(ethylene glycol) linkers by means of chemical ligation of nicked dumbbells requires a minimum of two A-T base pairs on either side of the nick. Molecular modeling indicates that the hexa(ethylene glycol) linker is sufficiently long to pemit formation of strain-free loop regions and B-DNA base pair domains. In contrast, the tri(ethylene glycoll is too short to permit Watson-Crick base pairing between the bases attached to the linker. The shorter linker distorts the duplex, resulting in fluxional behavior in which the base pairs adjacent to the linker and at the open end of the hairpin dissociate on the nanosecond time scale. The loss of interstrand binding energy caused by these fluctuations leads to a difference of ∼5 °C in melting temperature between EG3 and EG6 hairpins. An analysis of the fluxional behavior of the EG3 adjacent base-pair has been used to study the pathways for base flipping and base stacking, including the identification of rotated base (partially flipped) intermediates that have not been described previously for A-T base pairs.

Original languageEnglish
Pages (from-to)11415-11421
Number of pages7
JournalJournal of Physical Chemistry B
Volume112
Issue number36
DOIs
Publication statusPublished - Sep 11 2008

Fingerprint

dynamic stability
Ethylene Glycol
dynamic structural analysis
Structural dynamics
Ethylene glycol
DNA
deoxyribonucleic acid
ethylene
glycols
B-Form DNA
Molecular modeling
Binding energy
Melting point
Ethylene
Thermodynamic stability
thermal stability
binding energy
melting

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Materials Chemistry
  • Surfaces, Coatings and Films

Cite this

Effect of loop distortion on the stability and structural dynamics of DNA hairpin and dumbbell conjugates. / McCullagh, Martin; Zhang, Ligang; Karaba, Andrew H.; Zhu, Huihe; Schatz, George C; Lewis, Frederick D.

In: Journal of Physical Chemistry B, Vol. 112, No. 36, 11.09.2008, p. 11415-11421.

Research output: Contribution to journalArticle

McCullagh, Martin ; Zhang, Ligang ; Karaba, Andrew H. ; Zhu, Huihe ; Schatz, George C ; Lewis, Frederick D. / Effect of loop distortion on the stability and structural dynamics of DNA hairpin and dumbbell conjugates. In: Journal of Physical Chemistry B. 2008 ; Vol. 112, No. 36. pp. 11415-11421.
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