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

28 Citations (Scopus)

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

Fingerprint

G-Quadruplexes
Electrospray ionization
Phase stability
Electrospray Ionization Mass Spectrometry
Molecular Dynamics Simulation
Tandem Mass Spectrometry
Mass spectrometry
Molecular dynamics
Gases
Free energy
DNA
Computer simulation
Ammonium Compounds
Ions

ASJC Scopus subject areas

  • Structural Biology
  • Spectroscopy

Cite this

Gas-Phase Stability of G-quadruplex DNA Determined by Electrospray Ionization Tandem Mass Spectrometry and Molecular Dynamics Simulations. / Mazzitelli, Carolyn L.; Wang, Junmei; Smith, Suncerae I.; Brodbelt, Jennifer S.

In: Journal of the American Society for Mass Spectrometry, Vol. 18, No. 10, 10.2007, p. 1760-1773.

Research output: Contribution to journalArticle

@article{6bf5651dd2444bb79e7637b11cecdf1a,
title = "Gas-Phase Stability of G-quadruplex DNA Determined by Electrospray Ionization Tandem Mass Spectrometry and Molecular Dynamics Simulations",
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.",
author = "Mazzitelli, {Carolyn L.} and Junmei Wang and Smith, {Suncerae I.} and Brodbelt, {Jennifer S.}",
year = "2007",
month = "10",
doi = "10.1016/j.jasms.2007.07.008",
language = "English (US)",
volume = "18",
pages = "1760--1773",
journal = "Journal of the American Society for Mass Spectrometry",
issn = "1044-0305",
publisher = "Springer New York",
number = "10",

}

TY - JOUR

T1 - Gas-Phase Stability of G-quadruplex DNA Determined by Electrospray Ionization Tandem Mass Spectrometry and Molecular Dynamics Simulations

AU - Mazzitelli, Carolyn L.

AU - Wang, Junmei

AU - Smith, Suncerae I.

AU - Brodbelt, Jennifer S.

PY - 2007/10

Y1 - 2007/10

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=34548688162&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34548688162&partnerID=8YFLogxK

U2 - 10.1016/j.jasms.2007.07.008

DO - 10.1016/j.jasms.2007.07.008

M3 - Article

C2 - 17719795

AN - SCOPUS:34548688162

VL - 18

SP - 1760

EP - 1773

JO - Journal of the American Society for Mass Spectrometry

JF - Journal of the American Society for Mass Spectrometry

SN - 1044-0305

IS - 10

ER -