Modeling structure, stability and flexibility of double-stranded RNAs in salt solutions

Jin, Lei; Shi, Yuexi; Feng, Chenjie; Tan, Ya-Lan; Tan, Zhi-Jie

doi:10.1101/332676

Cited by 4 publications

(10 citation statements)

References 95 publications

(160 reference statements)

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“…However, recent experiments also show that DNA and RNA duplexes are strikingly different in stretching and twist-stretch coupling: 1) RNA duplex is significantly softer than DNA in stretching (i.e., stretch modulus S $350-600 pN and $1000-1500 pN for RNA and DNA duplexes (30,31,34), respectively); and 2) DNA duplex has an apparently negative twist-stretch coupling, whereas such twist-stretch coupling is apparently positive for RNA duplex (31). Later, all-atom MD simulations have been performed to understand the striking differences in stretching and twist-stretch coupling between DNA and RNA duplexes, and such differences are attributed to their different helical B-form and A-form structures (38)(39)(40)(41)(42)(43)(44)(45)(46). However, the structural flexibility of the DRH duplex has not been quantitatively characterized via either singlemolecule techniques or all-atom MD simulations, especially on stretching and twist-stretch coupling, which can be sensitive to helical structures of nucleic acids (16,(47)(48)(49)(50)(51).…”

Section: Introductionmentioning

confidence: 99%

Structural Flexibility of DNA-RNA Hybrid Duplex: Stretching and Twist-Stretch Coupling

Liu

Kun

Bao

et al. 2019

Biophysical Journal

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DNA-RNA hybrid (DRH) duplexes play essential roles during the replication of DNA and the reverse transcription of RNA viruses, and their flexibility is important for their biological functions. Recent experiments indicated that A-form RNA and B-form DNA have a strikingly different flexibility in stretching and twist-stretch coupling, and the structural flexibility of DRH duplex is of great interest, especially in stretching and twist-stretch coupling. In this work, we performed microsecond allatom molecular dynamics simulations with new AMBER force fields to characterize the structural flexibility of DRH duplex in stretching and twist-stretch coupling. We have calculated all the helical parameters, stretch modulus, and twist-stretch coupling parameters for the DRH duplex. First, our analyses on structure suggest that the DRH duplex exhibits an intermediate conformation between A-and B-forms and closer to A-form, which can be attributed to the stronger rigidity of the RNA strand than the DNA strand. Second, our calculations show that the DRH duplex has the stretch modulus of 834 5 34 pN and a very weak twiststretch coupling. Our quantitative analyses indicate that, compared with DNA and RNA duplexes, the different flexibility of the DRH duplex in stretching and twist-stretch coupling is mainly attributed to its apparently different basepair inclination in the helical structure.

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Section: Introductionmentioning

confidence: 99%

Structural Flexibility of DNA-RNA Hybrid Duplex: Stretching and Twist-Stretch Coupling

Liu

Kun

Bao

et al. 2019

Biophysical Journal

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“…For simplicity, the three beads are placed at the positions of existing atoms (i.e., P, C4’, and N1 for pyrimidine or N9 for purine) (Fig. 1) and are treated as van der Waals spheres with the radii of 1.9Å, 1.7Å and 2.2 Å, respectively (65,69). One unit negative charge (- e ) is placed on the center of P bead to describe the highly charged nature of DNA.…”

Section: Methodsmentioning

confidence: 99%

“…Afterward, the simulation of a DNA system with a given monovalent/divalent ion condition is performed from a high temperature (e.g., 120℃) to the target temperature (e.g., room/body temperature). At each temperature, conformational changes are accomplished via the translation and pivot moves, which have been demonstrated to be rather efficient in sampling conformations of polymers (77,78), and the changes are accepted or rejected according to the standard Metropolis algorithm (65,69). The equilibrium conformations at different temperatures during the cooling process are used to analyze the stability of the DNA.…”

Section: Methodsmentioning

confidence: 99%

“…To improve the simulation efficiency for dsDNA with low strand concentrations c s (e.g., <0.1mM), the MC simulations were performed at a relatively high strand concentration c s h (e.g., 1mM), and the fraction ( f (T; c s )) of denatured base pairs at lower c s can be calculated by that ( f (T; c s h )) at c s h (69,79,80) where λ = c s h / c s . Furthermore, for a dsDNA with a two-state transition, the melting temperature T m ( c s ) at c s can be directly obtained from T m ( c s h ) based on Eqs.…”

Section: Methodsmentioning

confidence: 99%

“…Although several of the existing models such as 3SPN, oxDNA, TIS, and NARES-2P have taken the electrostatic interactions into account using the Debye-Huckel approximation or mean-field multipole–multipole potentials and reproduced some monovalent salt-dependent structural properties (e.g., persistence length, torsional stiffness or melting temperatures) of DNAs (45,48,50,57), quantitatively predicting the 3D structure and thermodynamic stability for DNA including both ssDNA and dsDNA in ion solutions (especially divalent ions) from the sequence is still an unresolved problem. Recently, we have proposed a three-bead CG model to simulate RNA folding from the sequence, and with an implicit electrostatic potential, the model can make reliable predictions on 3D structures and stability for RNA hairpins, pseudoknots, and kissing complexes in ion solutions (65–69). However, due to the differences in geometry, base stacking strength, and flexibility between DNA and RNA, the present model cannot be directly used to simulate DNA folding.…”

Section: Introductionmentioning

confidence: 99%

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Ab initio predictions for 3D structure and stability of single- and double-stranded DNAs in ion solutions

Tan

Zhang

et al. 2022

Preprint

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The three-dimensional (3D) structure and stability of DNA are essential to understand/control their biological functions and aid the development of novel materials. In this work, we present a coarse-grained (CG) model for DNA based on the RNA CG model proposed by us, to predict 3D structures and stability for both dsDNA and ssDNA from the sequence. Combined with a Monte Carlo simulated annealing algorithm and CG force fields involving the sequence-dependent base-pairing/stacking interactions and an implicit electrostatic potential, the present model successfully folds 20 dsDNAs (≤52nt) and 20 ssDNAs (≤74nt) into the corresponding native-like structures just from their sequences, with an overall mean RMSD of 3.4Å from the experimental structures. For DNAs with various lengths and sequences, the present model can make reliable predictions on stability, e.g., for 27 dsDNAs with/without bulge/internal loops and 24 ssDNAs including pseudoknot, the mean deviation of predicted melting temperatures from the corresponding experimental data is only ~2.0℃. Furthermore, the model also quantificationally predicts the effects of monovalent or divalent ions on the structure stability of ssDNAs/dsDNAs.Author SummaryTo determine 3D structures and quantify stability of single- (ss) and double-stranded (ds) DNAs is essential to unveil the mechanisms of their functions and to further guide the production and development of novel materials. Although many DNA models have been proposed to reproduce the basic structural, mechanical, or thermodynamic properties of dsDNAs based on the secondary structure information or preset constraints, there are very few models can be used to investigate the ssDNA folding or dsDNA assembly from the sequence. Furthermore, due to the polyanionic nature of DNAs, metal ions (e.g., Na+ and Mg2+) in solutions can play an essential role in DNA folding and dynamics. Nevertheless, ab initio predictions for DNA folding in ion solutions are still an unresolved problem. In this work, we developed a novel coarse-grained model to predict 3D structures and thermodynamic stabilities for both ssDNAs and dsDNAs in monovalent/divalent ion solutions from their sequences. As compared with the extensive experimental data and available existing models, we showed that the present model can successfully fold simple DNAs into their native-like structures, and can also accurately reproduce the effects of sequence and monovalent/divalent ions on structure stability for ssDNAs including pseudoknot and dsDNAs with/without bulge/internal loops.

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FebRNA: An automated fragment-ensemble-based model for building RNA 3D structures

Zhou¹,

Wang²,

Yu³

et al. 2022

Biophysical Journal

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Modeling structure, stability and flexibility of double-stranded RNAs in salt solutions

Cited by 4 publications

References 95 publications

Structural Flexibility of DNA-RNA Hybrid Duplex: Stretching and Twist-Stretch Coupling

Structural Flexibility of DNA-RNA Hybrid Duplex: Stretching and Twist-Stretch Coupling

Ab initio predictions for 3D structure and stability of single- and double-stranded DNAs in ion solutions

FebRNA: An automated fragment-ensemble-based model for building RNA 3D structures

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