The pathway of oligomeric DNA melting investigated by molecular dynamics simulations

Ka Yiu Wong, Bernard Pettitt

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Details of the reaction coordinate for DNA melting are fundamental to much of biology and biotechnology. Recently, it has been shown experimentally that there are at least three states involved. To clarify the reaction mechanism of the melting transition of DNA, we perform 100-ns molecular dynamics simulations of a homo-oligomeric, 12-basepair DNA duplex, d(A12)·d(T 12), with explicit salt water at 400 K. Analysis of the trajectory reveals the various biochemically important processes that occur on different timescales. Peeling (including fraying from the ends), searching for Watson-Crick complements, and dissociation are recognizable processes. However, we find that basepair searching for Watson-Crick complements along a strand is not mechanistically tied to or directly accessible from the dissociation steps of strand melting. A three-step melting mechanism is proposed where the untwisting of the duplex is determined to be the major component of the reaction coordinate at the barrier. Though the observations are limited to the characteristics of the system being studied, they provide important insight into the mechanism of melting of other more biologically relevant forms of DNA, which will certainly differ in details from those here.

Original languageEnglish (US)
Pages (from-to)5618-5626
Number of pages9
JournalBiophysical Journal
Volume95
Issue number12
DOIs
StatePublished - Dec 15 2008
Externally publishedYes

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Nucleic Acid Denaturation
Molecular Dynamics Simulation
Freezing
compound A 12
DNA
Biotechnology
Salts
Water

ASJC Scopus subject areas

  • Biophysics

Cite this

The pathway of oligomeric DNA melting investigated by molecular dynamics simulations. / Wong, Ka Yiu; Pettitt, Bernard.

In: Biophysical Journal, Vol. 95, No. 12, 15.12.2008, p. 5618-5626.

Research output: Contribution to journalArticle

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