Publication details
Structural dynamics of possible late-stage intermediates in folding of quadruplex DNA studied by molecular simulations
| Authors | |
|---|---|
| Year of publication | 2013 |
| Type | Article in Periodical |
| Magazine / Source | Nucleic Acids Research |
| MU Faculty or unit | |
| Citation | |
| web | http://nar.oxfordjournals.org/content/41/14/7128 |
| Doi | http://dx.doi.org/10.1093/nar/gkt412 |
| Field | Physical chemistry and theoretical chemistry |
| Keywords | HUMAN TELOMERIC DNA; TETRAMOLECULAR G-QUADRUPLEXES; PARTICLE MESH EWALD; AMBER FORCE-FIELD; NUCLEIC-ACIDS; CRYSTAL-STRUCTURE; BIOMOLECULAR SIMULATIONS; INTERACTION POTENTIALS; FORMATION PATHWAYS; SOLUTION INSIGHTS |
| Attached files | |
| Description | 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. |
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