Simulating the Entropic Collapse of Coarse-Grained Chromosomes

TL;DR

This study uses coarse-grained molecular dynamics simulations to demonstrate that depletion forces alone can induce the collapse of flexible chromosomal DNA, modeling the process as a continuous phase transition.

Contribution

It introduces a coarse-grained simulation model and a theoretical framework showing depletion-induced attraction causes chromosome collapse as a continuous phase transition.

Findings

Depletion forces are sufficient for chromosome collapse.

Collapse occurs at predicted depletant volume fractions.

Collapse is a continuous phase transition.

Abstract

Depletion forces play a role in the compaction and de-compation of chromosomal material in simple cells but it remains debatable whether they are sufficient to account for chromosomal collapse. We present coarse-grained molecular dynamics simulations, which reveal that depletion-induced attraction is sufficient to cause the collapse of a flexible chain of large structural monomers immersed in a bath of smaller depletants. These simulations use an explicit coarse-grained computational model that treats both the supercoiled DNA structural monomers and the smaller protein crowding agents as combinatorial, truncated Lennard-Jones spheres. By presenting a simple theoretical model, we quantitatively cast the action of depletants on supercoiled bacterial DNA as an effective solvent quality. The rapid collapse of the simulated flexible chromosome at the predicted volume fraction of depletants is a continous phase transition. Additional physical effects to such simple chromosome models, such as enthalpic interactions between structural monomers or chain rigidity, are required if the collapse is to be a first-order phase transition.