Speaker
Description
Guanine-rich DNA sequences are capable to form non-canonical four-stranded secondary structures called G-quadruplexes (GQs). They are prevalent in gene promoters or telomeres, where they play role in key biological functions, such as maintenance of genome integrity, transcription, replication or epigenetic regulation. GQ formation is involved in development of genomic diseases such as some cancers of neuro-pathologies, as well as in viral infections, which makes them an attractive pharmacological target.
Despite the existing large amount of experimental work and classical and enhanced sampling molecular dynamics studies, complete picture of the folding process of the GQs is still unclear. In order to get further insights into the folding process of parallel GQs, we have explored the folding mechanism of the 15-nt DNA GQ d[(GGGA)3GGG] using all-atom Well-Tempered Metadynamic (WT-MetaD) in combination with REST2 (Replica Exchange with Solute Tempering) method in explicit solvent. While the single nucleotide loops are very likely to form the propeller arrangement, the only GQ topology accessible for the selected sequence is the parallel topology. Here, we analysed the folding process of the GQ by including all potential folding pathways along the previously suggested folding general mechanism from hairpin via triplex to quadruplex. The proposed procedure and obtained results presented in this work could help to better understand formation of the parallel GQ from fully unfolded state and can lead to design simulations of the folding of other complex systems
