4 research outputs found
Force unfolding kinetics of RNA using optical tweezers. II. Modeling experiments
By exerting mechanical force it is possible to unfold/refold RNA molecules
one at a time. In a small range of forces, an RNA molecule can hop between the
folded and the unfolded state with force-dependent kinetic rates. Here, we
introduce a mesoscopic model to analyze the hopping kinetics of RNA hairpins in
an optical tweezers setup. The model includes different elements of the
experimental setup (beads, handles and RNA sequence) and limitations of the
instrument (time lag of the force-feedback mechanism and finite bandwidth of
data acquisition). We investigated the influence of the instrument on the
measured hopping rates. Results from the model are in good agreement with the
experiments reported in the companion article (1). The comparison between
theory and experiments allowed us to infer the values of the intrinsic
molecular rates of the RNA hairpin alone and to search for the optimal
experimental conditions to do the measurements. We conclude that long handles
and soft laser traps represent the best conditions to extract rate estimates
that are closest to the intrinsic molecular rates. The methodology and
rationale presented here can be applied to other experimental setups and other
molecules.Comment: PDF file, 32 pages including 9 figures plus supplementary materia
Prediction of RNA Secondary Structure Including Kissing Hairpin Motifs
Theis C, Janssen S, Giegerich R. Prediction of RNA Secondary Structure Including Kissing Hairpin Motifs. In: Moulton V, Singh M, eds. Algorithms in Bioinformatics. 10th international workshop (WABI 2010), proceedings. Lecture Notes in Bioinformatics. Vol 6293. Berlin: Springer; 2010: 52-64.We present three heuristic strategies for folding RNA sequences into secondary structures including kissing hairpin motifs. The new idea is to construct a kissing hairpin motif from an overlay of two simple canonical pseudoknots. The difficulty is that the overlay does not satisfy Bellman's Principle of Optimality, and the kissing hairpin cannot simply be built from optimal pseudoknots. Our strategies have time/space complexities of O(n^4)/O(n^2), O(n^4)/O(n^3), and O(n^5)/O(n^2). All strategies have been implemented in the program pKiss and were evaluated against known structures. Surprisingly, our simplest strategy performs best. As it has the same complexity as the previous algorithm for simple pseudoknots, the overlay idea opens a way to construct a variety of practically useful algorithms for pseudoknots of higher topological complexity within O(n^4) time and O(n^2) space