The synergy between protein positioning and DNA elasticity: energy minimization of protein-decorated DNA minicircles

TL;DR

This paper introduces a new mesoscale energy minimization method to analyze how protein binding influences DNA deformation and positioning, revealing cooperative effects between DNA elasticity and protein-induced structural changes.

Contribution

A novel computational approach for optimizing protein-decorated DNA conformations considering elastic energy and spatial constraints.

Findings

Protein binding affects DNA deformation and positioning.

Mechanical stress influences protein placement on DNA.

Proteins modulate and broadcast mechanical stress along DNA.

Abstract

The binding of proteins onto DNA contributes to the shaping and packaging of genome as well as to the expression of specific genetic messages. With a view to understanding the interplay between the presence of proteins and the deformation of DNA involved in such processes, we developed a new method to minimize the elastic energy of DNA fragments at the mesoscale level. Our method makes it possible to obtain the optimal pathways of protein-decorated DNA molecules for which the terminal base pairs are spatially constrained. We focus in this work on the deformations induced by selected architectural proteins on circular DNA. We report the energy landscapes of DNA minicircles subjected to different levels of torsional stress and containing one or two proteins as functions of the chain length and spacing between the proteins. Our results reveal cooperation between the elasticity of the double helix and the structural distortions of DNA induced by bound proteins. We find that the imposed mechanical stress influences the placement of proteins on DNA and that, the proteins, in turn, modulate the mechanical stress and thereby broadcast their presence along DNA.