Explaining the striking difference in twist-stretch coupling between DNA and RNA: A comparative molecular dynamics analysis

Liebl, Korbinian; Dršata, Tomáš; Lankaš, Filip; Lipfert, Jan; Zacharias, Martin

doi:10.1093/nar/gkv1028

Cited by 63 publications

(137 citation statements)

References 63 publications

Supporting

Mentioning

123

Contrasting

Order By: Relevance

“…2B) showed that as the force increases, DNA overwinds and RNA unwinds. Although counterintuitive, this behavior is in agreement with previous experimental and theoretical works (2,3,5,19). The slope of a linear fit to the helical twist data provided a measurement of −g=CS (Fig.…”

Section: Resultssupporting

confidence: 91%

“…We performed all-atom MD simulations using the 16-mer dsDNA and dsRNA molecules used by Liebl et al (19). Molecules were neutralized with 30 sodium counter-ions and placed in a cubic box with dimensions of ∼80 Å × 80 Å × 80 Å, which was then filled with explicit water molecules.…”

Section: Resultsmentioning

confidence: 99%

“…This limitation is especially important for the small forces (below 20 pN) at which most biological processes occur (16). The analysis of single-molecule force extension data with a continuum mechanics approach, the so-called elastic rod model (17,18), reveals two particularly striking results: the threefold softer stretching response of dsRNA compared with dsDNA (6) and the opposite sign of the twist-stretch coupling (2,3,5,19). Ad hoc model extensions, such as the addition of an outer helical wire (2), and several models at the base-pair level (5,20) have been proposed to rationalize some of these results.…”

mentioning

confidence: 99%

“…A satisfactory explanation may involve differences in the atomic-scale structure that are beyond a continuum mechanics analysis (19,21).…”

mentioning

confidence: 99%

“…MD can access the atomic detail of an NA structure (22)(23)(24)(25) and provide information about the mechanical response of the chain as a whole (19,23,(26)(27)(28)(29). One common approach to address this problem is to determine the elastic parameters of a given NA chain through thermal fluctuations at the equilibrium of an unrestrained sequence (19,30,31). However, this approach cannot explore extensions corresponding to large force regimes.…”

mentioning

confidence: 99%

See 4 more Smart Citations

Understanding the mechanical response of double-stranded DNA and RNA under constant stretching forces using all-atom molecular dynamics

Marín-González

Vilhena

Pérez

et al. 2017

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

152

View full text Add to dashboard Cite

Multiple biological processes involve the stretching of nucleic acids (NAs). Stretching forces induce local changes in the molecule structure, inhibiting or promoting the binding of proteins, which ultimately affects their functionality. Understanding how a force induces changes in the structure of NAs at the atomic level is a challenge. Here, we use all-atom, microsecond-long molecular dynamics to simulate the structure of dsDNA and dsRNA subjected to stretching forces up to 20 pN. We determine all of the elastic constants of dsDNA and dsRNA and provide an explanation for three striking differences in the mechanical response of these two molecules: the threefold softer stretching constant obtained for dsRNA, the opposite twist-stretch coupling, and its nontrivial force dependence. The lower dsRNA stretching resistance is linked to its more open structure, whereas the opposite twist-stretch coupling of both molecules is due to the very different evolution of molecules' interstrand distance with the stretching force. A reduction of this distance leads to overwinding in dsDNA. In contrast, dsRNA is not able to reduce its interstrand distance and can only elongate by unwinding. Interstrand distance is directly correlated with the slide base-pair parameter and its different behavior in dsDNA and dsRNA traced down to changes in the sugar pucker angle of these NAs.

show abstract

Section: Resultssupporting

confidence: 91%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

“…A satisfactory explanation may involve differences in the atomic-scale structure that are beyond a continuum mechanics analysis (19,21).…”

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Understanding the mechanical response of double-stranded DNA and RNA under constant stretching forces using all-atom molecular dynamics

Marín-González

Vilhena

Pérez

et al. 2017

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

152

View full text Add to dashboard Cite

show abstract

Understanding the Structural Elasticity of RNA and DNA: All‐Atom Molecular Dynamics

Zhang

Yan

Huang

et al. 2022

Advcd Theory and Sims

View full text Add to dashboard Cite

Nucleic acids play essential roles in some biological processes and nanotechnology. Understanding their structural elasticity is very important for biological functions. Differences in structural elasticity of RNA and DNA duplexes are investigated by all‐atom molecular dynamics in this work. Two models double‐strand (ds) B‐DNA and A‐RNA short sequences are used. For two typical sequences, bending persistence length, stretch, and twist modulus are analyzed and compared in detail. These results demonstrate that dsDNA has a smaller bending persistence length value than dsRNA, however, the former has about 2.6 times stretch modulus than the latter one and the twist modulus in the former is smaller than the latter. Furthermore, the microstructural parameter analysis indicates that the inclination angle of a single base pair and the dihedral angle between two bases in a base pair, as well as the slide between adjacent base pairs, influences the structural elasticities of these two types of nucleic acids. Results also show that the dsDNA has a positive stretch‐twist coupling parameter while the dsRNA has a negative stretch‐twist coupling parameter. Results offer research comprehensive comparing and understanding about structural elasticity of RNA and DNA and provide novel perspectives for grasping nucleic acids' elastic properties.

show abstract

Structure and Internal Dynamics of Short RNA Duplexes Determined by a Combination of Pulsed EPR Methods and MD Simulations

Gauger,

Heinz,

Halbritter

et al. 2024

Angewandte Chemie

View full text Add to dashboard Cite

We used EPR spectroscopy to characterize the structure of RNA duplexes and their internal twist, stretch and bending motions. We prepared eight 20 base‐pair long RNA duplexes containing the rigid spin‐label Çm, a cytidine analogue, at two positions and acquired orientation‐selective PELDOR/DEER data. By using different frequency bands (X‐, Q‐, G‐band), detailed information about the distance and orientation of the labels was obtained and provided insights into the global conformational dynamics of the RNA duplex. We used 19F Mims ENDOR experiments on three singly Çm and singly fluorine labeled RNA duplexes to determine the exact position of the Çm spin label in the helix. In a quantitative comparison to MD simulations of RNA with and without Çm spin labels, we found that state‐of‐the‐art force fields with explicit parameterization of the spin label were able to describe the conformational ensemble present in our experiments. The MD simulations further confirmed that the Çm spin labels are excellent mimics of cytidine inducing only small local changes in the RNA structure. Çm spin labels are thus ideally suited for high‐precision EPR experiments to probe the structure and, in conjunction with MD simulations, motions of RNA.

show abstract

Explaining the striking difference in twist-stretch coupling between DNA and RNA: A comparative molecular dynamics analysis

Cited by 63 publications

References 63 publications

Understanding the mechanical response of double-stranded DNA and RNA under constant stretching forces using all-atom molecular dynamics

Understanding the mechanical response of double-stranded DNA and RNA under constant stretching forces using all-atom molecular dynamics

Understanding the Structural Elasticity of RNA and DNA: All‐Atom Molecular Dynamics

Structure and Internal Dynamics of Short RNA Duplexes Determined by a Combination of Pulsed EPR Methods and MD Simulations

Contact Info

Product

Resources

About