Predicting RNA pseudoknot folding thermodynamics

Cao, Song; Chen, Shi‐Jie

doi:10.1093/nar/gkl346

Cited by 143 publications

(202 citation statements)

References 75 publications

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“…In contrast to the diversity in the shapes and chemical characters of the building blocks of proteins, the four nts are all aromatic bases with similar chemical properties, thus making the interactions highly promiscuous. The low specificity of the interactions results in populations of alternate structures during the folding process (18-21).To understand the inherent sequence-dependent variations in RNA folding, we performed coarse-grained simulations of three pseudoknots, which are involved in ribosomal frameshifting (22)(23)(24)(25) and telomerase activity (26). Simulations using the Three Interaction Site (TIS) model for RNA (27) compare well with the available experimentally determined thermodynamic transitions.…”

mentioning

confidence: 99%

Assembly mechanisms of RNA pseudoknots are determined by the stabilities of constituent secondary structures

Cho

Pincus

Thirumalai

2009

Proc. Natl. Acad. Sci. U.S.A.

109

156

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Understanding how RNA molecules navigate their rugged folding landscapes holds the key to describing their roles in a variety of cellular functions. To dissect RNA folding at the molecular level, we performed simulations of three pseudoknots (MMTV and SRV-1 from viral genomes and the hTR pseudoknot from human telomerase) using coarse-grained models. The melting temperatures from the specific heat profiles are in good agreement with the available experimental data for MMTV and hTR. The equilibrium free energy profiles, which predict the structural transitions that occur at each melting temperature, are used to propose that the relative stabilities of the isolated helices control their folding mechanisms. Kinetic simulations, which corroborate the inferences drawn from the free energy profiles, show that MMTV folds by a hierarchical mechanism with parallel paths, i.e., formation of one of the helices nucleates the assembly of the rest of the structure. The SRV-1 pseudoknot, which folds in a highly cooperative manner, assembles in a single step in which the preformed helices coalesce nearly simultaneously to form the tertiary structure. Folding occurs by multiple pathways in the hTR pseudoknot, the isolated structural elements of which have similar stabilities. In one of the paths, tertiary interactions are established before the formation of the secondary structures. Our work shows that there are significant sequence-dependent variations in the folding landscapes of RNA molecules with similar fold. We also establish that assembly mechanisms can be predicted using the stabilities of the isolated secondary structures.kinetic partitioning mechanism ͉ parallel pathways ͉ ribosomal frameshifting ͉ RNA folding T he RNA folding problem has taken center stage in molecular biology because these molecules play a vital role in a variety of cellular functions. The percentage of the transcribed noncoding sequences in mice and human genomes exceed 90% (1), and the functional importance of the rest of the noncoding RNA is now only beginning to be understood (2). The noncoding roles of ribosomal RNA (rRNA) and transfer RNA (tRNA) are well known, but the discovery of ribozymes (RNA enzymes) has sparked an intense search for the functional roles of the rest of the noncoding RNA molecules (2, 3), which include catalysis, replication, transcriptional and translational regulation, and ligand binding (4), just to name a few. Consequently, it is important to determine the mechanisms by which RNA molecules fold so that a deeper understanding of the structure-function relationship can emerge.Although great progress has been made in understanding of how RNA molecules fold (5Ϫ10) global principles that determine the sequence dependent folding mechanisms have not fully emerged. It is argued that RNA folding mechanisms must be inherently simple because of the apparent separation in the energy scales that describe the different levels of structural organization (11). Furthermore, RNA molecules are constructed from only four nucleotides (nts), ...

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mentioning

confidence: 99%

Assembly mechanisms of RNA pseudoknots are determined by the stabilities of constituent secondary structures

Cho

Pincus

Thirumalai

2009

Proc. Natl. Acad. Sci. U.S.A.

109

156

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“…[44] Kinefold predicts the structures of pseudoknots with topological and geometrical constraints through a long-time-scale RNA folding simulation, [45] which follows the stochastic closing and opening of individual RNA helices . In addition, the thermodynamic parameters of pseudoknots loop can also be derived from a lattice model [40,47,48] and based on which, the Vfold predicts the free energy landscapes of pseudoknots. [40,48] …”

Section: Free Energy-based Methodsmentioning

confidence: 99%

“…In addition, the thermodynamic parameters of pseudoknots loop can also be derived from a lattice model [40,47,48] and based on which, the Vfold predicts the free energy landscapes of pseudoknots. [40,48] …”

Section: Free Energy-based Methodsmentioning

confidence: 99%

RNA structure prediction: Progress and perspective

Shi¹,

Wu²,

Wang³

et al. 2014

Chinese Phys. B

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Many recent exciting discoveries have revealed the versatility of RNAs and their impo rtance in a variety of cellular functions which are strongly coupled to RNA structures. To understand the functions of RNAs, some structure prediction models have been developed in recent years. In this review, the progress in computational models for RNA structure prediction is introduced and the distinguishing features of many outstanding algorithms are discussed, emphasizing three dimensional (3D) structure prediction. A promising coarse-grained model for predicting RNA 3D structure, stability and salt effect is also introduced briefly. Finally, we discuss the major challenges in the RNA 3D structure modeling.

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“…4,[20][21][22][23][24][25][26][27] These methods, especially the method based on the explicit conformation enumeration, 23 have led to several useful predictions for pseudoknot structures and folding stabilities. For a simple canonical H-type pseudoknot ͑Fig.…”

Section: Free Energy Model For Mg-like Structuresmentioning

confidence: 99%

“…First, unlike the simulation approaches, the Vfold model enables statistical mechanical calculations based on the complete ensemble of the reduced conformations. 4,9,23,27 Second, it provides a reliable lowresolution structural model, which can serve as a scaffold for further all-atom refinement through molecular dynamics computations. …”

Section: Loop-helix Connectionmentioning

confidence: 99%

Computing the conformational entropy for RNA folds

Liu

Chen

2010

The Journal of Chemical Physics

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We develop a polymer physics-based method to compute the conformational entropy for RNA tertiary folds, namely, conformations consisting of multiple helices connected through ͑cross-linked͒ loops. The theory is based on a virtual bond conformational model for the nucleotide chain. A key issue in the calculation of the entropy is how to treat the excluded volume interactions. The weak excluded volume interference between the different loops leads to the decomposition of the whole structure into a number of three-body building blocks, each consisting of a loop and two helices connected to the two ends of the loop. The simple construct of the three-body system allows an accurate computation for the conformational entropy for each building block. The assembly of the building blocks gives the entropy of the whole structure. This approach enables treatment of molten globule-like folds ͑partially unfolded tertiary structures͒ for RNAs. Extensive tests against experiments and exact computer enumerations indicate that the method can give accurate results for the entropy. The method developed here provides a solid first step toward a systematic development of a theory for the entropy and free energy landscape for complex tertiary folds for RNAs and proteins.

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Predicting RNA pseudoknot folding thermodynamics

Cited by 143 publications

References 75 publications

Assembly mechanisms of RNA pseudoknots are determined by the stabilities of constituent secondary structures

Assembly mechanisms of RNA pseudoknots are determined by the stabilities of constituent secondary structures

RNA structure prediction: Progress and perspective

Computing the conformational entropy for RNA folds

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