8,992 research outputs found
Ab initio RNA folding
RNA molecules are essential cellular machines performing a wide variety of
functions for which a specific three-dimensional structure is required. Over
the last several years, experimental determination of RNA structures through
X-ray crystallography and NMR seems to have reached a plateau in the number of
structures resolved each year, but as more and more RNA sequences are being
discovered, need for structure prediction tools to complement experimental data
is strong. Theoretical approaches to RNA folding have been developed since the
late nineties when the first algorithms for secondary structure prediction
appeared. Over the last 10 years a number of prediction methods for 3D
structures have been developed, first based on bioinformatics and data-mining,
and more recently based on a coarse-grained physical representation of the
systems. In this review we are going to present the challenges of RNA structure
prediction and the main ideas behind bioinformatic approaches and physics-based
approaches. We will focus on the description of the more recent physics-based
phenomenological models and on how they are built to include the specificity of
the interactions of RNA bases, whose role is critical in folding. Through
examples from different models, we will point out the strengths of
physics-based approaches, which are able not only to predict equilibrium
structures, but also to investigate dynamical and thermodynamical behavior, and
the open challenges to include more key interactions ruling RNA folding.Comment: 28 pages, 18 figure
Prediction of RNA pseudoknots by Monte Carlo simulations
In this paper we consider the problem of RNA folding with pseudoknots. We use
a graphical representation in which the secondary structures are described by
planar diagrams. Pseudoknots are identified as non-planar diagrams. We analyze
the non-planar topologies of RNA structures and propose a classification of RNA
pseudoknots according to the minimal genus of the surface on which the RNA
structure can be embedded. This classification provides a simple and natural
way to tackle the problem of RNA folding prediction in presence of pseudoknots.
Based on that approach, we describe a Monte Carlo algorithm for the prediction
of pseudoknots in an RNA molecule.Comment: 22 pages, 14 figure
A complex adaptive systems approach to the kinetic folding of RNA
The kinetic folding of RNA sequences into secondary structures is modeled as
a complex adaptive system, the components of which are possible RNA structural
rearrangements (SRs) and their associated bases and base pairs. RNA bases and
base pairs engage in local stacking interactions that determine the
probabilities (or fitnesses) of possible SRs. Meanwhile, selection operates at
the level of SRs; an autonomous stochastic process periodically (i.e., from one
time step to another) selects a subset of possible SRs for realization based on
the fitnesses of the SRs. Using examples based on selected natural and
synthetic RNAs, the model is shown to qualitatively reproduce characteristic
(nonlinear) RNA folding dynamics such as the attainment by RNAs of alternative
stable states. Possible applications of the model to the analysis of properties
of fitness landscapes, and of the RNA sequence to structure mapping are
discussed.Comment: 23 pages, 4 figures, 2 tables, to be published in BioSystems (Note:
updated 2 references
Mechanical unfolding of RNA: From hairpins to structures with internal multiloops
Mechanical unfolding of RNA structures, ranging from hairpins to ribozymes,
using laser optical tweezer (LOT) experiments have begun to reveal the features
of the energy landscape that cannot be easily explored using conventional
experiments. Upon application of constant force (), RNA hairpins undergo
cooperative transitions from folded to unfolded states whereas subdomains of
ribozymes unravel one at a time. Here, we use a self-organized polymer (SOP)
model and Brownian dynamics simulations to probe mechanical unfolding at
constant force and constant-loading rate of four RNA structures of varying
complexity. Our work shows (i) the response of RNA to force is largely
determined by the native structure; (ii) only by probing mechanical unfolding
over a wide range of forces can the underlying energy landscape be fully
explored.Comment: 26 pages, 6 figures, Biophys. J. (in press
Pathways and kinetic barriers in mechanical unfolding and refolding of RNA and proteins
Using self-organized polymer models, we predict mechanical unfolding and
refolding pathways of ribo-zymes, and the green fluorescent protein. In
agreement with experiments, there are between six and eight unfolding
transitions in the Tetrahymena ribozyme. Depending on the loading rate, the
number of rips in the force-ramp unfolding of the Azoarcus ribozymes is between
two and four. Force-quench refolding of the P4-P6 subdomain of the Tetrahymena
ribozyme occurs through a compact intermediate. Subsequent formation of
tertiary contacts between helices P5b-P6a and P5a/P5c-P4 leads to the native
state. The force-quench refolding pathways agree with ensemble experiments. In
the dominant unfolding route, the N-terminal a helix of GFP unravels first,
followed by disruption of the N terminus b strand. There is a third
intermediate that involves disruption of three other strands. In accord with
experiments, the force-quench refolding pathway of GFP is hierarchic, with the
rate-limiting step being the closure of the barrel.Comment: 33 pages 7 figure
A new procedure to analyze RNA non-branching structures
RNA structure prediction and structural motifs analysis are challenging tasks in the investigation of RNA function. We propose a novel procedure to detect structural motifs shared between two RNAs (a reference and a target). In particular, we developed two core modules: (i) nbRSSP_extractor, to assign a unique structure to the reference RNA encoded by a set of non-branching structures; (ii) SSD_finder, to detect structural motifs that the target RNA shares with the reference, by means of a new score function that rewards the relative distance of the target non-branching structures compared to the reference ones. We integrated these algorithms with already existing software to reach a coherent pipeline able to perform the following two main tasks: prediction of RNA structures (integration of RNALfold and nbRSSP_extractor) and search for chains of matches (integration of Structator and SSD_finder)
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