RNA folding pathways in stop motion

@article{Bottaro2016RNAFP,
  title={RNA folding pathways in stop motion},
  author={Sandro Bottaro and Alejandro Gil-Ley and Giovanni Bussi},
  journal={Nucleic Acids Research},
  year={2016},
  volume={44},
  pages={5883 - 5891}
}
We introduce a method for predicting RNA folding pathways, with an application to the most important RNA tetraloops. The method is based on the idea that ensembles of three-dimensional fragments extracted from high-resolution crystal structures are heterogeneous enough to describe metastable as well as intermediate states. These ensembles are first validated by performing a quantitative comparison against available solution nuclear magnetic resonance (NMR) data of a set of RNA tetranucleotides… 

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References

SHOWING 1-10 OF 70 REFERENCES
Computer Folding of RNA Tetraloops? Are We There Yet?
TLDR
This work uses Replica Exchange Molecular Dynamics with the recent reparameterization of AMBER RNA force field to study the folding of RNA hairpins containing representatives UNCG and GNRA TL, and identifies a misfolded-bulged state of GNRATL, which shares many structural features with the X-ray structure of GN RA TL in the complex with restrictocin.
High-resolution reversible folding of hyperstable RNA tetraloops using molecular dynamics simulations
TLDR
The ability to recapitulate the signature noncanonical interactions of the three most abundant hyperstable stem loop motifs represents a significant milestone to the accurate prediction of RNA tertiary structure using unbiased all-atom molecular dynamics simulations.
Delineation of folding pathways of a β-sheet miniprotein.
TLDR
This work compares LSDMap to two previously developed approaches for the characterization of the configurational landscape associated with the folding dynamics of a three-stranded antiparallel β-sheet peptide, termed Beta3s and finds that the results from LSDMap are consistent with analysis based on transition networks and allow a coherent interpretation of metastable states and folding pathways.
Elucidating Molecular Motion through Structural and Dynamic Filters of Energy-Minimized Conformer Ensembles
TLDR
The results introduce a protocol to construct viable dynamic trajectories for RNA molecules that accord well with experimental NMR data and support the notion that the motions of the helical portions of this small RNA can be described by a relatively small number of discrete conformations exchanging over time scales longer than 1 μs.
ATP dependent NS3 helicase interaction with RNA: insights from molecular simulations
TLDR
The analysis of the hydrogen bond network and of the non-equilibrium trajectories indicates an ATP-dependent stabilization of one of the protein conformers, and enthalpy calculations suggest that entropic effects might be crucial for the stabilization of the experimentally observed structures.
A Probabilistic Model of RNA Conformational Space
TLDR
A probabilistic model of RNA structure that allows efficient sampling of RNA conformations in continuous space, and with associated probabilities is offered: a theoretical and practical solution for a major bottleneck on the way to routine prediction and simulation ofRNA structure and dynamics in atomic detail.
Exploring the energy landscape of a small RNA hairpin.
TLDR
An analysis of three variants shows that one of the intermediate RNA structures is a stacking-related trap affected by stem but not loop modification, while the other is an early intermediate that forms some stem and loop structure.
Performance of Molecular Mechanics Force Fields for RNA Simulations: Stability of UUCG and GNRA Hairpins.
TLDR
A critical assessment of a broad set of MD simulations of UUCG, GAGA, and GAAA tetraloops using various force fields reveals several problems which show that these force fields are not able to retain all characteristic structural features (structural signature) of the studied tetraloop.
Structural fidelity and NMR relaxation analysis in a prototype RNA hairpin.
TLDR
This work provides a comprehensive and detailed comparison of state of the art MD simulations against a wide variety of solution NMR measurements and pins G9-G10 backbone conformations as a locus of discrepancies between experiment and simulation.
...
...