Untwisting of Double-Stranded DNA and RNA Investigated by Molecular Dynamics Simulations

Abstract

The response of dsDNA and dsRNA to torsional stress influences many of their biological functions, including binding by proteins, transcription initiation and genome packaging. So far, the twist flexibility of DNA and RNA has been studied comparatively with single-molecule experiments. However, while these studies capture the global deformability of duplexes with a length of several thousand base pairs (bp), detailed insight into conformational changes on the base pair level remains elusive. We performed all-atom Molecular Dynamics (MD) simulations on 15 bp long DNA and RNA duplexes at femtosecond resolution. Employing an advanced sampling method based on a torsion-like restraining potential, we were able to untwist the molecules to induce localized melting. The simulations allowed us to determine the relative free energy and structural changes as a function of the mean twist. Suppression of local bending has a strong influence on the onset of DNA melting. Significant differences in the response were also observed for DNA and RNA. The results can have important implications for understanding the mechanism of replication and transcription of DNA the function of RNA molecules.