Structural dynamics of possible late-stage intermediates in folding of quadruplex DNA studied by molecular simulations.
Nucleic Acids Res
; 41(14): 7128-43, 2013 Aug.
Article
en En
| MEDLINE
| ID: mdl-23700306
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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
ADN
/
G-Cuádruplex
/
Simulación de Dinámica Molecular
Límite:
Humans
Idioma:
En
Revista:
Nucleic Acids Res
Año:
2013
Tipo del documento:
Article
País de afiliación:
República Checa