Unveiling nucleosome dynamics: A comparative study using all-atom and coarse-grained simulations enhanced by principal component analysis

Abstract

The conformational dynamics of the DNA in the nucleosome may play a role in governing gene regulation and accessibility and impact higher-order chromatin structure. This study investigates nucleosome dynamics using both all-atom and coarse-grained (CG) molecular dynamics simulations, focusing on the SIRAH force field. Simulations are performed for two nucleosomal DNA sequences—alpha satellite palindromic and Widom-601—over 6 μs at physiological salt concentrations. A comparative analysis of structural parameters, such as groove widths and base pair geometries, reveals good agreement between atomistic and CG models, although CG simulations exhibit broader conformational sampling and greater breathing motion of DNA ends. Principal component analysis is applied to DNA structural parameters, revealing multiple free energy minima, especially in CG simulations. These findings highlight the potential of the SIRAH CG force field for studying large-scale nucleosome dynamics, offering insights into DNA repositioning and sequence-dependent behavior.