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(TG(4)T)](4), [d(T(2)G(3)T)](4), [d(G(4)T(4)G(4))](2), [d(T(2)AG(3))(2)](2), d(T(2)AG(3))(4), d(T(2)G(4))(4), and d(G(2)T(4))(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(TG(4)T)](4) and [d(T(2)G(3)T)](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 E(1/2) values, and the resulting order of relative stabilities was found to be [d(TG(4)T)](4) >> d(T(2)AG(3))(4) approximately d(T(2)G(4))(4) > [d(T(2)G(3)T)](4) > [d(T(2)AG(3))(2)](2) approximately d(G(2)T(4))(4) approximately [d(G(4)T(4)G(4))](2.) The stabilities from the E(1/2) 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(G(4)T(4)G(4))](2), which had the lowest E(1/2) 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.
authors.affiliation: Department of Chemistry and Biochemistry, University of Texas at Austin, Austin, Texas 78712, USA.
authors.forename: Carolyn L
authors.initials: CL
authors.lastname: Mazzitelli
authors.forename: Junmei
authors.initials: J
authors.lastname: Wang
authors.forename: Suncerae I
authors.initials: SI
authors.lastname: Smith
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Brodbelt
mesh_terms: D003198:Computer Simulation; D004247:DNA / Q000737:chemistry*; D054856:G-Quadruplexes; D005740:Gases / Q000737:chemistry*; D008956:Models, Chemical; D008958:Models, Molecular; D044367:Phase Transition; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D005740:Gases; D004247:DNA