title: Implication of the solvent effect, metal ions and topology in the electronic structure and hydrogen bonding of human telomeric G-quadruplex DNA.
abstract: We present a first-principles density functional study elucidating the effects of solvent, metal ions and topology on the electronic structure and hydrogen bonding of 12 well-designed three dimensional G-quadruplex (G4-DNA) models in different environments. Our study shows that the parallel strand structures are more stable in dry environments and aqueous solutions containing K(+) ions within the tetrad of guanine but conversely, that the anti-parallel structure is more stable in solutions containing the Na(+) ions within the tetrad of guanine. The presence of metal ions within the tetrad of the guanine channel always enhances the stability of the G4-DNA models. The parallel strand structures have larger HOMO-LUMO gaps than antiparallel structures, which are in the range of 0.98 eV to 3.11 eV. Partial charge calculations show that sugar and alkali ions are positively charged whereas nucleobases, PO4 groups and water molecules are all negatively charged. Partial charges on each functional group with different signs and magnitudes contribute differently to the electrostatic interactions involving G4-DNA and favor the parallel structure. A comparative study between specific pairs of different G4-DNA models shows that the Hoogsteen OH and NH hydrogen bonds in the guanine tetrad are significantly influenced by the presence of metal ions and water molecules, collectively affecting the structure and the stability of G4-DNA.
authors.affiliation: Department of Physics and Astronomy, University of Missouri-Kansas City, Kansas City, MO 64110, USA. Chingw@umkc.edu.
authors.forename: Lokendra
authors.initials: L
authors.lastname: Poudel
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA and Department of Radiology, Case Western Reserve University, Cleveland, OH 44106, USA and Department of Materials Science and Engineering, Case Western Reserve University, Cleveland, OH 44106, USA and Department of Macromolecular Science and Engineering, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Nicole F
authors.initials: NF
authors.lastname: Steinmetz
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA and Department of Materials Science and Engineering, Case Western Reserve University, Cleveland, OH 44106, USA and Department of Macromolecular Science and Engineering, Case Western Reserve University, Cleveland, OH 44106, USA and Department of Physics, University of Massachusetts, Amherst, Massachusetts 01003, USA.
authors.forename: Roger H
authors.initials: RH
authors.lastname: French
authors.affiliation: Department of Physics, University of Massachusetts, Amherst, Massachusetts 01003, USA.
authors.forename: V Adrian
authors.initials: VA
authors.lastname: Parsegian
authors.affiliation: Department of Physics, University of Massachusetts, Amherst, Massachusetts 01003, USA and Department of Theoretical Physics, J. Stefan Institute, SI-1000 Ljubljana, Slovenia and Department of Physics, Faculty of Mathematics and Physics, University of Ljubljana, SI-1000 Ljubljana, Slovenia.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Podgornik
authors.affiliation: Department of Physics and Astronomy, University of Missouri-Kansas City, Kansas City, MO 64110, USA. Chingw@umkc.edu.
authors.forename: Wai-Yim
authors.initials: WY
authors.lastname: Ching
mesh_terms: D004247:DNA / Q000737:chemistry*; D054856:G-Quadruplexes; D006801:Humans; D006860:Hydrogen Bonding; D008670:Metals; D008958:Models, Molecular; D016615:Telomere
chemical_list: D008670:Metals; D004247:DNA