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
Articles

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.

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Copyright information

© American Society for Mass Spectrometry 2007

Authors and Affiliations

  • Carolyn L. Mazzitelli
    • 1
  • Junmei Wang
    • 2
  • Suncerae I. Smith
    • 1
  • Jennifer S. Brodbelt
    • 1
  1. 1.Department of Chemistry and BiochemistryUniversity of Texas at AustinAustinUSA
  2. 2.Encysive Pharmaceuticals Inc.HoustonUSA

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