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.

Figure 1

(A) Illustration of the contour lengths L of the 30-bp dsRNA and dsDNA taken from the 40-bp dsRNA and dsDNA with excluding 5 bp at each end, as described in the Materials and Methods. (B) The contour length and cumulative H-twist versus MD running time (600 ns) for the central 30-bp dsRNA and dsDNA. Here, the (central) light-red lines and light-blue lines represent the average contour length and cumulative H-twist over every 2 ns of dsRNA and dsDNA. To see this figure in color, go online.

Figure 2

Normalized distributions of contour length L for the central 30-bp dsRNA and dsDNA. To see this figure in color, go online.

Figure 3

Normalized distributions of rise (A) and H-rise (B) averaged per conformation for dsRNA and dsDNA from the statistical analyses of MD trajectories. To see this figure in color, go online.

Figure 4

(A and B) Illustrations of rise, H-rise, and inclination between adjacent basepairs and central helical axis. The representations for rise and H-rise are shown as red short lines, and inclination is defined as the angle between the vector of rise and central helical axis. It is shown that the way of basepairing/stacking causes a distinct difference in H-rise between dsRNA and dsDNA. (C and D) Normalized distributions of inclination (C) and slide (D) averaged per conformation for dsRNA and dsDNA from the statistical analyses of MD trajectories. (E) Correlations between H-rise and inclination for dsRNA and dsDNA from the statistical analyses of MD trajectories. Notably, inclination decreases with increasing H-rise. To see this figure in color, go online.

Figure 5

(A and B) Relationships between H-rise and H-twist that are directly extracted from the MD trajectories for dsRNA and dsDNA. (C and D) Relationships between H-rise and twist that are also directly extracted from the MD trajectories for dsRNA and dsDNA. Here, the recorded H-twist, twist, and H-rise are taken as the average H-twist, twist, and H-rise within intervals of 0.1°. Such treatment may cause a slight change in the range of recorded H-rise. Error bars are obtained as standard errors of the averages in each interval. In each panel, the raw data are shown as a density landscape with normalized probability. To see this figure in color, go online.

Figure 6

(A) Correlations between roll and twist for dsRNA and dsDNA from the statistical analyses of MD trajectories. (B) Relationship between roll and twist is shown as a schematic model of one basepair step. Because the sugar-phosphate backbone (dark green) is approximately inextensible, an increase in roll (absolute value) will induce a decrease in twist. (C) Correlations between roll and H-rise for dsRNA and dsDNA from the statistical analyses of MD trajectories. (D) Correlations between roll and inclination for dsRNA and dsDNA from the statistical analyses of MD trajectories. To see this figure in color, go online.

Figure 7

(A) Detailed representation of the relationship among the three quantities: twist, H-twist, and inclination. (B) A diagrammatic model of the global structures of dsRNA (left) and dsDNA (right) for illustrating twist and H-twist. Here, we omit showing the basepair step. If basepair inclination exists, H-twist would be larger than twist, and twist and H-twist would gradually become overlapped with the decrease of inclination angle to zero. The inclination angle is ∼15.9° for dsRNA and ∼7.8° for dsDNA. (C) Normalized distributions of H-twist (solid line) and twist (dashed line) for the 30-bp dsRNA (red) and dsDNA (blue), respectively. To see this figure in color, go online.

Figure 8

(A) Normalized distributions of contour length L for the central 10-bp dsRNA and dsDNA, respectively. (B) Relationships between H-rise and H-twist directly extracted from the MD trajectories for the central 10 bp of the 16-bp dsRNA and dsDNA. To see this figure in color, go online.