Explaining the striking difference in twist-stretch coupling between DNA and RNA: A comparative molecular dynamics analysis.
Bottom Line: Similar results are also found in simulations that include an external torque to induce over- or unwinding of DNA and RNA.Overwinding of RNA results in more compact conformations with a narrower major groove and consequently reduced helical extension.Overwinding of DNA decreases the size of the minor groove and the resulting positive base pair inclination leads to a slender and more extended helical structure.
Affiliation: Physik-Department T38, Technische Universität München, James-Franck-Strasse, D-85748 Garching, Germany.Show MeSH
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Mentions: In case of RNA canonical starting values for twist (32.5°) and rise (2.6 Å) were used combined with an x-disp = −4.4 Å and incl = 17.5° close to the mean values seen in the MD simulations. In addition, two deformed start states with more negative x-disp = −4.8 Å and reduced incl = 10.5° or x-disp = −4.0 Å and incl = 25.5°, respectively, were energy minimized keeping x-disp and inclination locked. Indeed, the sterically optimized RNA locked to a more negative x-disp and reduced inclination resulted in an unwinding of the helix and increased helical rise (Table 1) and an open major groove (Figure 8). The opposite was observed for the relaxation of the other deformed start structure compared to the (relaxed) reference structure generating an overwound (overtwisted) RNA molecules with also strongly reduced helical rise and reduced major groove (very similar to the results of the MD simulations, Figure 8). Hence, the twist-stretch coupling observed for RNA in MD simulations can also be achieved by using x-disp and incl as input variables (allowing twist and rise to adopt the sterically most favorable combination) demonstrating the interplay between the helical variables. It is important to note that the same energy minimization results (to within an RMSD of < 0.3 Å) were achieved for A-DNA versus A-RNA. This provides strong evidence that the helical topology, rather than the presence of an additional hydroxyl group or the uridine instead of adenine base in RNA, mediates the opposite twist-stretch coupling of B-DNA and A-RNA.
Affiliation: Physik-Department T38, Technische Universität München, James-Franck-Strasse, D-85748 Garching, Germany.