Molecular Dynamics Simulations of a Nucleosome and Free DNA

Abstract

Nucleosomes organize the folding of DNA into chromatin and significantly influence transcription, replication, regulation and repair. All atom molecular dynamics simulations of a nucleosome and of its 146 basepairs of DNA free in solution have been conducted. DNA helical parameters are extracted from each trajectory to compare the conformation, effective force constants, persistence length measures, and fluctuations of nucleosomal DNA to free DNA. A method for disassembling and reconstructing the conformation and dynamics of the nucleosome using Fourier analysis is presented. Results indicate that the superhelical path of DNA in the nucleosome is irregular. Long length variations in the conformation of nucleosomal DNA are identified other than those associated with helix repeat. These variations are required to create a proposed tetrasome conformation or to qualitatively reconstruct the 1.75 turns of the nuclesomal superhelix. Free DNA achieves enough bend and shear in solution to create an ideal nucleosome superhelix, but these deformations are not organized so the conformation is essentially linear. Reconstruction of free DNA using selected long wavelength variations in conformation can produce either a left-handed or a right-handed superhelix. DNA is less flexible in the nucleosome than when free in solution, however such measures are length scale dependent.