Advances in RNA molecular dynamics: a simulator's guide to RNA force fields

@article{Vangaveti2017AdvancesIR,
  title={Advances in RNA molecular dynamics: a simulator's guide to RNA force fields},
  author={Sweta Vangaveti and Srivathsan Vembanur Ranganathan and Alan A. Chen},
  journal={Wiley Interdisciplinary Reviews: RNA},
  year={2017},
  volume={8}
}
Molecular simulations have become an essential tool for biochemical research. When they work properly, they are able to provide invaluable interpretations of experimental results and ultimately provide novel, experimentally testable predictions. Unfortunately, not all simulation models are created equal, and with inaccurate models it becomes unclear what is a bona fide prediction versus a simulation artifact. RNA models are still in their infancy compared to the many robust protein models that… 
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39 Citations
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Methods Citations
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39 Citations

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Challenges with Simulating Modified RNA: Insights into Role and Reciprocity of Experimental and Computational Approaches
TLDR
This review provides an overview of the state of MDS of modified RNA, focusing on the challenges in parameterization of RNA modifications as well as insights into relevant reference experiments necessary for their calibration.
Toward Convergence in Folding Simulations of RNA Tetraloops: Comparison of Enhanced Sampling Techniques and Effects of Force Field Modifications.
TLDR
This work studies two RNA tetraloops, namely the GAGA and UUCG motifs, and demonstrates that the combination of REST2 with well-tempered metadynamics (ST-MetaD) achieves good convergence on a timescale of 5-10 μs per replica, improving the sampling efficiency by at least 2 orders of magnitude.
Fine-tuning of the AMBER RNA Force Field with a New Term Adjusting Interactions of Terminal Nucleotides
TLDR
The combination of gHBfix with tHBfix significantly improves the behavior of RNA TNs during well-converged enhanced-sampling simulations, and suggests that future tuning of some other ff terms might be useful.
Fine-tuning of the AMBER RNA Force Field with a New Term Adjusting Interactions of Terminal Nucleotides.
TLDR
Combination of gHBfix with tHBfix significantly improves the behavior of RNA TNs during well-converged enhanced-sampling simulations using replica exchange with solute tempering and has a clear potential to improve modeling of key biochemical processes, where interactions of RNA single stranded ends are involved.
Towards Convergence in Folding Simulations of RNA Tetraloops: Comparison of Enhanced Sampling Techniques and Effects of Force Field Corrections
TLDR
It is demonstrated that replica exchange solute tempering simulations with 12-16 replicas do not show any sign of convergence even when extended to time scale of 120 μs per replica, and combination of REST2 with well-tempered metadynamics (ST-MetaD) achieves good convergence on a time-scale of 5-10 μsper replica, improving the sampling efficiency by at least two orders of magnitude.
Improving the Performance of the RNA Amber Force Field by Tuning the Hydrogen-Bonding Interactions
TLDR
A general ff term (gHBfix) that can selectively fine-tune non-bonding interaction terms in RNA ffs, in particular the H-bonds is introduced that has a clear promising potential to improve the ff performance while avoiding introduction of major new imbalances.
Improving the Performance of the Amber RNA Force Field by Tuning the Hydrogen-Bonding Interactions.
TLDR
A general ff term that can selectively fine-tune nonbonding interaction terms in RNA ffs, in particular, the H bonds is introduced, and particular gHBfix parameters to modify the AMBER RNA ff are proposed.
Chemically Accurate Relative Folding Stability of RNA Hairpins from Molecular Simulations
TLDR
A novel method to identify where replica free energies diverge along the reaction coordinate, thus indicating where additional sampling would most improve convergence is reported, which suggests analo-gous simulations could be used predictively.
Exploring RNA structure and dynamics through enhanced sampling simulations.
The mechanism of RNA base fraying: Molecular dynamics simulations analyzed with core-set Markov state models.
TLDR
A method for determining biomolecular dynamics employing core-set Markov state models constructed using an advanced clustering technique is introduced and validated on previously reported simulations of RNA base fraying.
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