The critical effect of polarization on the dynamical structure of guanine quadruplex DNA

Guanine quadruplex DNA (G-DNA), found in eukaryotic telomeres and recently in non-telomeric genomic DNA, plays important biological roles and their structures are being explored as potential targets for therapeutic intervention. Since the quadruplex structure of G-DNA is stabilized by cations, electrostatic interaction is expected to play important roles in the dynamical structure of G-DNA. In current work, MD simulation was carried out to study the dynamical structure of a special G-DNA (with sequence d(G₄T₄G ₄)) complexed with five K⁺ ions. In order to properly include polarization in MD simulation, a new set of polarized nucleic acid specific charge based on fragment quantum chemistry calculation was developed for G-DNA. Our study showed that polarization of the nucleobases by K ⁺ enhanced electrostatic attraction between the base and ions. This increased attractive interaction is critical to stabilizing the stem-loop junction ions in G-DNA. Without this polarization effect, as in MD simulation using a standard (nonpolarizable) force field, the top and bottom cations escaped into the solvent within just a few nanoseconds. Furthermore, an incorrect bifurcated bonding geometry of G-DNA, found in previous MD simulation study under a standard force field but not observed in experiments, disappeared in the present stimulation using the new polarized force field. The current study bridged an important gap between the simulation study and experimental observation on the dynamical structure of G-DNA.