Advances in <scp>RNA</scp> molecular dynamics: a simulator's guide to <scp>RNA</scp> force fields

Vangaveti, Sweta; Ranganathan, S.; Chen, Alan

doi:10.1002/wrna.1396

Cited by 63 publications

(72 citation statements)

References 75 publications

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“…Molecular dynamics (MD) simulations have become a very important tool for studies of biomolecular systems such as nucleic acids with routine access to micro-or even millisecond timescales. [1][2][3][4][5][6][7] MD simulations are often instrumental for understanding and clarifying experimental results and for obtaining a more complete picture of their biological implications.…”

Section: Introductionmentioning

confidence: 99%

Improving The Performance Of The Amber Rna Force Field By Tuning The Hydrogen-Bonding Interactions

Kührová

Mlýnský

Zgarbová

et al. 2018

Preprint

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# authors contributed equally * corresponding authors email: sponer@ncbr.muni.cz and pavel.banas@upol.cz KEYWORDS RNA, force field, MD simulation, enhanced sampling, folding, tetraloop.Recent studies generated large conformational ensembles of TNs 14-15, 17, 28-29, 31, 33-34 and TLs 14-15, 17, 28-29, 31, 35, 53-56 in order to assess the performance of RNA ffs. They showed that the available RNA ffs have persisting deficiencies causing, e.g., (i) shifts of the backbone dihedral angles to non-native values, (ii) problems with the c-dihedral angle distribution, and (iii) over-populated SPh and BPh hydrogen bond interactions. 15,25,55 Some of those studies also suggested potential directions for ff improvement, which included modifications of backbone dihedral terms, van der Waals (vdW) radii and charges, RNA interaction with solvent/ions (adjustments of Lennard-Jones parameters typically accompanied by modifications of the Lennard-Jones combining rules via nonbonded fix, NBfix, to balance the RNA-solvent interaction) and enforced distributions from solution experiments. 14, 17, 29-31, 53, 57-60 Computer folding of UNCG TLs appears to be much more challenging than folding of GNRA TLs and description of TNs, 15,35,53,55,61 as for the latter two systems some partial successes have been reported. Note that there have been repeated past claims in the literature about successful folding of RNA TLs in simulations. However, the claims were not confirmed by independent research groups, as extensively reviewed in Ref. 4 . The performance and possible shortcomings of another recently released ff 60 are discussed as part of this work.Previously, we have shown that at least two different imbalances likely contribute to the (in)correct folded/unfolded free-energy balance of TNs and TLs. The first problem was excessive stabilization of the unfolded ssRNA structure by intramolecular BPh and SPh interactions. 62 The excessive binding of 2'-hydroxyl groups (2'-OH) towards phosphate nonbridging oxygens (nbO) was reported earlier 27, 58 and could be partially reduced by using alternative phosphate oxygen parameters developed by Case et al. 63 in combination with the OPC 64 explicit solvent water model. 14 However, the OPC water model was shown to destabilize

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Section: Introductionmentioning

confidence: 99%

Improving The Performance Of The Amber Rna Force Field By Tuning The Hydrogen-Bonding Interactions

Kührová

Mlýnský

Zgarbová

et al. 2018

Preprint

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“…tRNA Arg1 ICG and tRNA Arg2 ICG differ only in their position-32 modification status; unmodified tRNA Arg2 ICG binds CGC, CGU and CGA arginine codons in agreement with the predictions of the Wobble Hypothesis, but s 2 C 32 -modified tRNA Arg1 ICG is incapable of wobble binding to CGA [131,219]. The structural basis of the restrictive effect of 2-thiocytidine at position 32 stems from a tendency of the thio modification to contribute to a global, destabilizing dehydration of the ASL under the structural conditions where its conformation has already been perturbed to adapt to a spatially broad adenosine-inosine purine-purine base pair in the wobble position of the anticodon-codon interface [220].…”

Section: Modifications At Position 32mentioning

confidence: 99%

Chemical and Conformational Diversity of Modified Nucleosides Affects tRNA Structure and Function

et al. 2017

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RNAs are central to all gene expression through the control of protein synthesis. Four major nucleosides, adenosine, guanosine, cytidine and uridine, compose RNAs and provide sequence variation, but are limited in contributions to structural variation as well as distinct chemical properties. The ability of RNAs to play multiple roles in cellular metabolism is made possible by extensive variation in length, conformational dynamics, and the over 100 post-transcriptional modifications. There are several reviews of the biochemical pathways leading to RNA modification, but the physicochemical nature of modified nucleosides and how they facilitate RNA function is of keen interest, particularly with regard to the contributions of modified nucleosides. Transfer RNAs (tRNAs) are the most extensively modified RNAs. The diversity of modifications provide versatility to the chemical and structural environments. The added chemistry, conformation and dynamics of modified nucleosides occurring at the termini of stems in tRNA’s cloverleaf secondary structure affect the global three-dimensional conformation, produce unique recognition determinants for macromolecules to recognize tRNAs, and affect the accurate and efficient decoding ability of tRNAs. This review will discuss the impact of specific chemical moieties on the structure, stability, electrochemical properties, and function of tRNAs.

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“…26, 42, 61, 62 The structure of the 5′GAGU/3′UGAG internal loop 44 suggests that 2×2 nt internal loops closed by GU pairs can provide additional benchmarks for testing that balance. 40 Optical melting experiments and 1D imino proton NMR spectra of the GU closed loops studied here reveal unexpected equilibria and structures that will challenge computations.…”

Section: Introductionmentioning

confidence: 99%

Surprising Sequence Effects on GU Closure of Symmetric 2 × 2 Nucleotide RNA Internal Loops

et al. 2018

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GU base pairs are important RNA structural motifs and often close loops. Accurate prediction of RNA structures relies upon understanding the interactions determining structure. The thermodynamics of some two-by-two nucleotide internal loops closed by GU pairs are not well understood. Here, several self-complementary oligonucleotide sequences expected to form duplexes with two-by-two nucleotide internal loops closed by GU pairs were investigated. Surprisingly, NMR revealed that many of the sequences exist in equilibrium between hairpin and duplex conformations. This equilibrium is not observed with loops closed by Watson-Crick pairs. To measure the thermodynamics of some two-by-two nucleotide internal loops closed by GU pairs, non-self-complementary sequences were designed that preclude formation of hairpins. The measured thermodynamics indicate that some internal loops closed by GU pairs are unusually unstable. This instability accounts for the observed equilibria between duplex and hairpin conformations. Moreover, it suggests that future three dimensional structures of loops closed by GU pairs may reveal interactions that unexpectedly destabilize folding.

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

Cited by 63 publications

References 75 publications

Improving The Performance Of The Amber Rna Force Field By Tuning The Hydrogen-Bonding Interactions

Improving The Performance Of The Amber Rna Force Field By Tuning The Hydrogen-Bonding Interactions

Chemical and Conformational Diversity of Modified Nucleosides Affects tRNA Structure and Function

Surprising Sequence Effects on GU Closure of Symmetric 2 × 2 Nucleotide RNA Internal Loops

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