Understanding the Relative Flexibility of RNA and DNA Duplexes: Stretching and Twist-Stretch Coupling

Abstract

The flexibility of double-stranded (ds) RNA and dsDNA is crucial for their biological functions. Recent experiments have shown that the flexibility of dsRNA and dsDNA can be distinctively different in the aspects of stretching and twist-stretch coupling. Although various studies have been performed to understand the flexibility of dsRNA and dsDNA, there is still a lack of deep understanding of the distinctive differences in the flexibility of dsRNA and dsDNA helices as pertains to their stretching and twist-stretch coupling. In this work, we have explored the relative flexibility in stretching and twist-stretch coupling between dsRNA and dsDNA by all-atom molecular dynamics simulations. The calculated stretch modulus and twist-stretch coupling are in good accordance with the existing experiments. Our analyses show that the differences in stretching and twist-stretch coupling between dsRNA and dsDNA helices are mainly attributed to their different (A- and B-form) helical structures. Stronger basepair inclination and slide in dsRNA is responsible for the apparently weaker stretching rigidity versus that of dsDNA, and the opposite twist-stretch coupling for dsRNA and dsDNA is also attributed to the stronger basepair inclination in dsRNA than in dsDNA. Our calculated macroscopic elastic parameters and microscopic analyses are tested and validated by different force fields for both dsRNA and dsDNA.

Identification of Myricetin as an Ebola Virus VP35–Double-Stranded RNA Interaction Inhibitor through a Novel Fluorescence-Based Assay

“…However, on the one side myricetin has been shown to intercalate into dsDNA at concentrations greater than 300 µM, hence 100-fold higher than the observed IC 50 value; on the other side, intercalation is considered more unlikely to happen in the case Biochemistry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 16 of dsRNA. In fact, dsRNA has a weaker stretching rigidity versus the one of dsDNA, due to the stronger basepair inclination and slide in dsRNA 97 . Such hypothesis is also unlikely given the fact that other flavonoinds with intercalating properties similar to myricetin, such as luteolin, are inactive in our assay (data not shown), further confirming that the myricetin effect can't be linked to a hypothetic dsRNA binding.…”

Molecular chains under tension: Thermal and mechanical activation of statistically interacting extension and contraction particles

“…Experimental, computational, and theoretical studies of mechanical and thermal responses of molecular chains to tension, torque, and environmental change continue to be confronted with new vistas and new challenges due to astonishing advances in nanoscale technology, notably single-molecule manipulation techniques [1][2][3][4][5][6]. The work reported here and in two related studies [7,8] aims to shed light on the statistical mechanics of molecular chains under tension and torque and in interaction with molecules of the embedding fluid medium by a methodology not hitherto applied to this field, yet well developed in other areas of one-dimensional structures.…”

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

“…8E. To avoid the end effect (94), the first and last 5 base pairs were excluded in our calculations and the bond vectors are selected as those over every 5 continuous base pairs (91).…”

“…In this section, we further employed the present model to examine the flexibility of a 40-bp RNA helix in ion solutions. The sequence of the dsRNA helix is 5’-CGACUCUACGGAAGGGCAUCCUUCGGGCAUCACUACGCGC-3’ with 57% CG content in its central 30-bp segment and the other chain is fully complementary to it, which is selected according to previous studies (85). First, we predicted the 3D structures for the dsRNA helix from the sequence at 25°C, and afterwards, we performed further simulations for the dsRNA helix at various ion conditions based on the predicted structures.…”