Stability and cations coordination of DNA and RNA 14-mer G-quadruplexes: a multiscale computational approach.
Molecular dynamics simulations have been used to study the differences between two DNA and RNA 14-mer quadruplexes of analogous sequences. Their structures present a completely different fold: DNA forms a bimolecular quadruplex containing antiparallel strands and diagonal loops; RNA forms an intrastrand parallel quadruplex containing a G-tetrad and an hexad, which dimerizes by hexad stacking. We used a multiscale computational approach combining classical Molecular dynamics simulations and density functional theory calculations to elucidate the difference in stability of the 2-folds and their ability in coordinating cations. The presence of 2'-OH groups in the RNA promotes the formation of a large number of intramolecular hydrogen bonds that account for the difference in fold and stability of the two 14-mers. We observe that the adenines in the RNA quadruplex play a key role in conserving the geometry of the hexad. We predict the cation coordination mode of the two quadruplexes, not yet observed experimentally, and we offer a rationale for the corresponding binding energies involved.
Pagano
Bruno
B
Dipartimento di Scienze Farmaceutiche, Università di Salerno, via Ponte Don Melillo, Fisciano (SA), I-84084, Italy.
Mattia
Carlo A
CA
Cavallo
Luigi
L
Uesugi
Seiichi
S
Giancola
Concetta
C
Fraternali
Franca
F