title: Folding pathways of human telomeric type-1 and type-2 G-quadruplex structures.
abstract: We have investigated new folding pathways of human telomeric type-1 and type-2 G-quadruplex conformations via intermediate hairpin and triplex structures. The stabilization energies calculated by ab initio methods evidenced the formation of a hairpin structure with Hoogsteen GG base pairs. Further calculations revealed that the G-triplet is more stable than the hairpin conformation and equally stable when compared to the G-tetrad. This indicated the possibility of a triplex intermediate. The overall folding is facilitated by K(+) association in each step, as it decreases the electrostatic repulsion. The K(+) binding site was identified by molecular dynamics simulations. We then focused on the syn/anti arrangement and found that the anti conformation of deoxyguanosine is more stable than the syn conformation, which indicated that folding would increase the number of anti conformations. The K(+) binding to a hairpin near the second lateral TTA loop was found to be preferable, considering entropic effects. Stacking of G-tetrads with the same conformation (anti/anti or syn/syn) is more stable than mixed stacking (anti/syn and vice versa). These results suggest the formation of type-1 and type-2 G-quadruplex structures with the possibility of hairpin and triplex intermediates.
authors.affiliation: Department of Chemistry, Graduate School of Science, Kyoto University, Kitashirakawa-oiwakecho, Sakyo-ku, Kyoto 606-8502, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Mashimo
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Yagi
authors.forename: Yuta
authors.initials: Y
authors.lastname: Sannohe
authors.forename: Arivazhagan
authors.initials: A
authors.lastname: Rajendran
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sugiyama
mesh_terms: D001483:Base Sequence; D017931:DNA Primers; D054856:G-Quadruplexes; D006801:Humans; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation; D055672:Static Electricity; D016615:Telomere; D013816:Thermodynamics
chemical_list: D017931:DNA Primers