SKM 2023 – wissenschaftliches Programm
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BP: Fachverband Biologische Physik
BP 11: Poster Session I
BP 11.21: Poster
Dienstag, 28. März 2023, 12:30–15:30, P1
RNA G-quadruplex folding is a multi-pathway process with a variety of short-lived intermediate states — •Marijana Ugrina1, Ines Burkhart2, Diana Müller2, Harald Schwalbe2, and Nadine Schwierz1 — 1University of Augsburg, Augsburg, Germany — 2Goethe University, Frankfurt am Main, Germany
The folding kinetics of regulatory RNAs is crucial for their function. Here, we provide molecular insights into the folding pathways of a G-quadruplex from telomeric repeat-containing RNA by combining all-atom molecular dynamics and coarse-grained simulations with circular dichroism experiments. The ion atmosphere surrounding the highly charged quadruplex plays a crucial role in folding. To correctly capture the electric double-layer in implicit solvent coarse-grained simulations, we develop a matching procedure based on all-atom simulations in explicit water. This procedure allows us to provide quantitative agreement between the experiments and simulations as judged by the number of native contacts at different salt concentrations and temperatures. Folding of the quadruplex is on the timescale of minutes and the coarse-grained simulations using the three-interactions site model are therefore ideal to resolve the folding pathways and intermediate states. The results reveal that the folding is sequential with each pathway passing through two transient, on-pathway intermediates: A hairpin and a triplex or double hairpin state. Since these intermediates are degenerate with at two to four alternative conformations per state, quadruplex folding is a multi-pathway process with high conformational entropy.