Anharmonic Torsional Stiffness of DNA Revealed under Small External Torques

TL;DR

This study uses molecular dynamics simulations to show that small external torques can significantly alter DNA's torsional stiffness, with sequence-specific effects that may influence gene regulation.

Contribution

It reveals how minor static untwisting affects DNA torsional stiffness differently depending on sequence, highlighting potential mechanisms for gene regulation.

Findings

Small static untwisting reduces torsional persistence length in GC DNA.

AT DNA shows a smaller, opposite effect on torsional stiffness.

Sequence-specific local torsional fluctuations can influence gene regulation.

Abstract

DNA supercoiling plays an important role in a variety of cellular processes. The torsional stress related with supercoiling may be also involved in gene regulation through the local structure and dynamics of the double helix. To check this possibility steady torsional stress was applied to DNA in the course of all-atom molecular dynamics simulations. It is found that small static untwisting significantly reduces the torsional persistence length ($l_t$) of GC-alternating DNA. For the AT-alternating sequence a smaller effect of the opposite sign is observed. As a result, the measured $l_t$ values are similar under zero stress, but diverge with untwisting. The effect is traced to sequence-specific asymmetry of local torsional fluctuations, and it should be small in long random DNA due to compensation. In contrast, the stiffness of special short sequences can vary significantly, which gives a simple possibility of gene regulation via probabilities of strong fluctuations. These results have important implications for the role of local DNA twisting in complexes with transcription factors.