title: Structural dynamics of possible late-stage intermediates in folding of quadruplex DNA studied by molecular simulations.
abstract: Explicit solvent molecular dynamics simulations have been used to complement preceding experimental and computational studies of folding of guanine quadruplexes (G-DNA). We initiate early stages of unfolding of several G-DNAs by simulating them under no-salt conditions and then try to fold them back using standard excess salt simulations. There is a significant difference between G-DNAs with all-anti parallel stranded stems and those with stems containing mixtures of syn and anti guanosines. The most natural rearrangement for all-anti stems is a vertical mutual slippage of the strands. This leads to stems with reduced numbers of tetrads during unfolding and a reduction of strand slippage during refolding. The presence of syn nucleotides prevents mutual strand slippage; therefore, the antiparallel and hybrid quadruplexes initiate unfolding via separation of the individual strands. The simulations confirm the capability of G-DNA molecules to adopt numerous stable locally and globally misfolded structures. The key point for a proper individual folding attempt appears to be correct prior distribution of syn and anti nucleotides in all four G-strands. The results suggest that at the level of individual molecules, G-DNA folding is an extremely multi-pathway process that is slowed by numerous misfolding arrangements stabilized on highly variable timescales.
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic, Královopolská 135, 612 65 Brno, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Stadlbauer
authors.forename: Miroslav
authors.initials: M
authors.lastname: Krepl
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Cheatham
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Koca
authors.forename: Jirí
authors.initials: J
authors.lastname: Sponer
mesh_terms: D004247:DNA / Q000737:chemistry*; D004277:DNA, Single-Stranded / Q000737:chemistry; D054856:G-Quadruplexes; D006801:Humans; D056004:Molecular Dynamics Simulation; D016615:Telomere / Q000737:chemistry
chemical_list: D004277:DNA, Single-Stranded; D004247:DNA