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Internet Electronic Journal of Molecular Design - IEJMD, ISSN 1538-6414, CODEN IEJMAT
| ABSTRACT - Internet Electron. J. Mol. Des. February 2006, Volume 5, Number 2, 79-88 |
Theoretical Study of G4-M+-G4 (M = Li, Na and K) Complexes: Structure,
Stability and Electrostatic Potential
Fancui Meng, Weiren Xu, and Chengbu Liu
Internet Electron. J. Mol. Des. 2006, 5, 79-88
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Abstract:
Guanine-rich DNA can form a G-quadruplex structure in the
presence of Na+ or K+ ions. These structures are important in the
design of DNA-interactive antitumour drugs, and the investigation
of structure and properties of G-quadruplex is currently an area of
major interest. Single guanine tetrad with metal ions has been
extensively studied previously, while in vivo the guanine tetrads
are mostly stacked, and thus the sandwiched structures of G4-M+-G4
need to be investigated. In this paper the "sandwich" models of
the metal ion (Li+, Na+ and K+) G-tetrads complexes have been
studied using ab initio and density functional theory methods. The
results show that with the increasing of the cation radius, the
structure of the G4-M+-G4 becomes looser and looser. Binding
energies indicate that the Li+ complex is the most stable one
without hydration effect correction, while the stability sequence
changes to K+ > Na+ > Li+
after considering the hydration effect,
which coincides with the experimental situation. The electrostatic
potential maps show that the optimal position of potassium in the
guanine quadruplex is intercalated between two guanine tetrads,
while the sandwich complexes of lithium and sodium are not the
optimal structure. Together with ion size and hydration, the
electrostatic potential of the sandwich guanine tetrads influence the
structural and energetic properties of the cation binding stacked guanine tetrads.
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