Informace o publikaci

Hairpins participating in folding of human telomeric sequence quadruplexes studied by standard and T-REMD simulations

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STADLBAUER Petr KUHROVÁ Petra BANÁŠ Pavel KOČA Jaroslav BUSSI Giovanni TRANTÍREK Lukáš OTYEPKA Michal ŠPONER Jiří

Rok publikování 2015
Druh Článek v odborném periodiku
Časopis / Zdroj Nucleic Acids Research
Fakulta / Pracoviště MU

Středoevropský technologický institut

Citace
www http://nar.oxfordjournals.org/content/43/20/9626.full.pdf+html
Doi http://dx.doi.org/10.1093/nar/gkv994
Obor Biochemie
Klíčová slova MOLECULAR-DYNAMICS SIMULATIONS; INTRAMOLECULAR DNA QUADRUPLEXES; PARTICLE MESH EWALD; AMBER FORCE-FIELD; G-TRACT LENGTH; NUCLEIC-ACIDS; REPLICA-EXCHANGE; K+ SOLUTION; ENERGY LANDSCAPE; STRUCTURAL DYNAMICS
Přiložené soubory
Popis DNA G-hairpins are potential key structures participating in folding of human telomeric guanine quadruplexes (GQ). We examined their properties by standard MD simulations starting from the folded state and long T-REMD starting from the unfolded state, accumulating similar to 130 mu s of atomistic simulations. Antiparallel G-hairpins should spontaneously form in all stages of the folding to support lateral and diagonal loops, with sub-mu s scale rearrangements between them. We found no clear predisposition for direct folding into specific GQ topologies with specific syn/anti patterns. Our key prediction stemming from the T-REMD is that an ideal unfolded ensemble of the full GQ sequence populates all 4096 syn/anti combinations of its four G-stretches. The simulations can propose idealized folding pathways but we explain that such few-state pathways may be misleading. In the context of the available experimental data, the simulations strongly suggest that the GQ folding could be best understood by the kinetic partitioning mechanism with a set of deep competing minima on the folding landscape, with only a small fraction of molecules directly folding to the native fold. The landscape should further include non-specific collapse processes where the molecules move via diffusion and consecutive random rare transitions, which could, e.g. structure the propeller loops.
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