# Inferring DNA Kinkability from Biased MD Simulations

## TL;DR

This paper uses simulations to study how DNA can form kinks under mechanical stress and identifies two distinct types of kinks based on their structural properties.

## Contribution

The study introduces a novel method using biased MD simulations to infer DNA kinkability and identifies sequence-dependent kink formation.

## Key findings

- Two types of DNA kinks are identified: twist-bend kinks and pure bend kinks.
- Free energy landscapes reveal sequence-dependent effects on kink formation.
- Twist-bend kinks are favored in negatively supercoiled DNA, while pure bend kinks occur in torsionally constrained DNA.

## Abstract

In several biological processes, such as looping, supercoiling,
and DNA–protein interactions, DNA is subject to very strong
deformations. While coarse-grained models often approximate DNA as
a smoothly bendable polymer, experimental and theoretical studies
have demonstrated that mechanical stress can induce localized kinks.
Here, we employ the Rigid Base Biasing of Nucleic Acids (RBB-NA) algorithm
to systematically probe the properties of highly deformed DNA in all-atom
simulations of short dodecamers. A simultaneous bias in bending (roll)
and twist is applied locally to two consecutive base pairs in the
center of the dodecamers. Using umbrella sampling, we construct free
energy landscapes that reveal sequence-dependent effects for kink
formation and quantify the energetic cost of kinking. We identify
distinct features in the free energy profiles highlighting anharmonic
effects, such as asymmetries in the positive vs negative roll. Our
analysis suggests two distinct kink types characterized either by
positive roll and undertwisting (twist-bend kinks) or by negative
roll without excess twist (pure bend kinks). The former are frequently
observed in DNA–protein structures and are expected to be favored
in vivo in negatively supercoiled chromosomes. The latter has been
observed in DNA simulations of minicircles and is favored in torsionally
constrained DNA.