Multiscale coarse-grained modelling of chromatin components: DNA and the nucleosome

Abstract

To model large biomolecular systems, such as cell and organelles an atomistic description is not currently achievable and is not generally practical. Therefore, simplified coarse-grained (CG) modelling becomes a necessity. One of the most important cellular components is chromatin, a large DNA-protein complex where DNA is highly compacted. Recent progress in coarse graining modelling of the major chromatin components, double helical DNA and the nucleosome core particle (NCP) is presented. First, general principles and approaches allowing rigorous bottom-to-top generation of interaction potentials in the CG models are presented. Then, recent CG models of DNA are reviewed and their adequacy is benchmarked against experimental data on the salt dependence of DNA flexibility (persistence length). Furthermore, a few recent CG models of the NCP are described and their application for studying salt-dependent NCP-NCP interaction is discussed. An example of a multiscale approach to CG modelling of chromatin is presented where interactions and self-assembly of thousands of NCPs in solution are observed.

Keywords: Computer simulations; DNA condensation; Inverse Monte Carlo; Macromolecular assembly; Polyelectrolytes.