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

Area of Science:

• Biophysics
• Computational Biology
• Structural Biology

Background:

• Double-stranded DNA (dsDNA) and RNA (dsRNA) exhibit complex conformational flexibility.
• Existing models fail to explain experimental findings on twist-stretch coupling differences between dsDNA and dsRNA.

Purpose of the Study:

• To investigate the molecular mechanisms behind the qualitatively different twist-stretch couplings observed in dsDNA and dsRNA.
• To reproduce and explain experimental results using computational simulations.

Main Methods:

• Unconstrained Molecular Dynamics (MD) simulations.
• Simulations incorporating external torque to induce DNA and RNA unwinding/overwinding.
• Detailed analysis of helical deformations, including helical rise and base pair inclination.

Main Results:

• MD simulations successfully reproduced the opposite twist-stretch coupling signs for dsDNA and dsRNA, aligning with experimental data.
• Simulations with applied torque confirmed these distinct behaviors.
• Analysis identified helical rise, base pair inclination, and displacement as key factors driving the observed correlations.

Conclusions:

• The interplay of specific helical deformations explains the divergent twist-stretch couplings in dsDNA and dsRNA.
• Overwinding RNA leads to compact structures with reduced extension due to major groove narrowing.
• Overwinding DNA results in extended structures due to minor groove changes and base pair inclination.