DNA Relaxation Dynamics in 1ID3 Yeast Nucleosome MD Simulation

Abstract

Nucleosomes are elemental structural units envolved in the formation of chromatin. Organization of chromatin has a profound effect on DNA transcription, replication, repair and recombination. Nucleosomes not only participate in the compaction of the genetic material but also regulate gene expression by controlling the accessibility of specific DNA binding sites to proteins. There are 33 crystal structures of nucleosomes currently available in the protein databank. Nucleosome typically consists of a 147 bp dsDNA wrapped around an octameric histone protein, (H2A.1-H2B.2)(H3-H4)2(H2A.1-H2B.2), in 1.65 left-handed superhelical turns. DNA interacts with histone octamer at 14 locations (every ∼10 bp), forming a total of ∼240 direct and indirect contacts and ∼120 hydrogen bonds. Molecular Dynamics simulation is a useful technique for exploring dynamics at interaction sites. We performed a 50 ns MD simulation of 1id3 yeast nucleosome and analyzed DNA motions in terms of calculated relaxation times and slopes of power law distributions for all 145 inter base pair steps. Relaxation times were found by fitting the autocorrelation functions of DNA helix parameters. Those for base pairs interacting with histone core could not be obtained due to the power law nature of dynamics at detected sites. Our results suggest that relaxation of DNA structure in the nucleosome is governed by two processess: 1) fast exponential decay (25 - 250 ps) followed by power law relaxation for base pairs that are more than 3.4 A away from the protein, and, 2) slow power law relaxation extending to 50 ns observed for base pairs interacting with histone subunit (less than 3.4 A away from protein). Proximity analysis confirms the presence of 14 histone-DNA interaction sites while autocorrelation and Fourier analysis proves to be useful for the studies of relaxation dynamics in nucleosomes.