Gas-Phase Stability of G-quadruplex DNA Determined by Electrospray Ionization Tandem Mass Spectrometry and Molecular Dynamics Simulations

Carolyn L. Mazzitelli, Junmei Wang, Suncerae I. Smith, Jennifer S. Brodbelt

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

The relative gas-phase stabilities of seven quadruplex DNA structures, [d(TG4T)]4, [d(T2G3T)]4, [d(G4T4G4)]2, [d(T2AG3)2]2, d(T2AG3)4, d(T2G4)4, and d(G2T4)4, were investigated using molecular dynamics simulations and electrospray ionization mass spectrometry (ESI-MS). MD simulations revealed that the G-quadruplexes maintained their structures in the gas phase although the G-quartets were distorted to some degree and ammonium ions, retained by [d(TG4T)]4 and [d(T2G3T)]4, played a key role in stabilizing the tetrad structure. Energy-variable collisional activated dissociation was used to assess the relative stabilities of each quadruplex based on E1/2 values, and the resulting order of relative stabilities was found to be [d(TG4T)]4 ≫ d(T2AG3)4 ∼ d(T2G4)4 > [d(T2G3T)]4 > [d(T2AG3)2]2 ∼ d(G2T4)4 ∼ [d(G4T4G4)]2. The stabilities from the E1/2 values generally paralleled the RMSD and relative free energies of the quadruplexes based on the MD energy analysis. One exception to the general agreement is [d(G4T4G4)]2, which had the lowest E1/2 value, but was determined to be the most stable quadruplex according to the free-energy analysis and ranked fourth based on the RMSD comparison. This discrepancy is attributed to differences in the fragmentation pathway of the quadruplex.

Original languageEnglish (US)
Pages (from-to)1760-1773
Number of pages14
JournalJournal of the American Society for Mass Spectrometry
Volume18
Issue number10
DOIs
StatePublished - Oct 2007

ASJC Scopus subject areas

  • Structural Biology
  • Spectroscopy

Fingerprint Dive into the research topics of 'Gas-Phase Stability of G-quadruplex DNA Determined by Electrospray Ionization Tandem Mass Spectrometry and Molecular Dynamics Simulations'. Together they form a unique fingerprint.

Cite this