Parallel G-triplexes and G-hairpins as potential transitory ensembles in the folding of parallel-stranded DNA G-Quadruplexes
| Autor: | Petra Kührová, Pavel Banáš, Jiří Šponer, Lukáš Trantírek, Lukáš Vicherek, Michal Otyepka, Petr Stadlbauer |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Guanine
DNA Single-Stranded Biology Molecular Dynamics Simulation 010402 general chemistry G-quadruplex 01 natural sciences 03 medical and health sciences chemistry.chemical_compound Molecular dynamics Genetics Molecule Animals Humans Nucleotide 030304 developmental biology chemistry.chemical_classification 0303 health sciences Base Sequence Energy landscape Computational Biology Single-molecule FRET DNA 0104 chemical sciences G-Quadruplexes Kinetics chemistry Nucleic acid Biophysics Nucleic Acid Conformation |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| Popis: | Guanine quadruplexes (G4s) are non-canonical nucleic acids structures common in important genomic regions. Parallel-stranded G4 folds are the most abundant, but their folding mechanism is not fully understood. Recent research highlighted that G4 DNA molecules fold via kinetic partitioning mechanism dominated by competition amongst diverse long-living G4 folds. The role of other intermediate species such as parallel G-triplexes and G-hairpins in the folding process has been a matter of debate. Here, we use standard and enhanced-sampling molecular dynamics simulations (total length of ∼0.9 ms) to study these potential folding intermediates. We suggest that parallel G-triplex per se is rather an unstable species that is in local equilibrium with a broad ensemble of triplex-like structures. The equilibrium is shifted to well-structured G-triplex by stacked aromatic ligand and to a lesser extent by flanking duplexes or nucleotides. Next, we study propeller loop formation in GGGAGGGAGGG, GGGAGGG and GGGTTAGGG sequences. We identify multiple folding pathways from different unfolded and misfolded structures leading towards an ensemble of intermediates called cross-like structures (cross-hairpins), thus providing atomistic level of description of the single-molecule folding events. In summary, the parallel G-triplex is a possible, but not mandatory short-living (transitory) intermediate in the folding of parallel-stranded G4. |
| Databáze: | OpenAIRE |
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