Structural flexibility of the nucleosome core particle at atomic resolution studied by molecular dynamics simulation

Comparative explicit solvent molecular dynamics (MD) simulations have been performs on a complete nucleasome core particle with and without N-terminal simulations was to study the dynamics of mobile elements such as histone N-terminal tails and how packing and DNA-bending influences the fine structure and dynamics of DNA. Except for the tails, histone and DNA molecules stayed on average close to the crystallographic start structure supporting the quality of the current force field approach. Despite the packing strain, no increase of transitions to noncanonical nucleic acid backbone conformations compared to regular B-DNA was observed. The pattern of kinks and bends along the DNA remained close to the experiment overall. In addition to the local dynamics, the simulations allowed the analysis of the superhelical mobility indicating a limited relative mobility of DATA segments separated by one superhelical turn (mean relative displacement of approximately +/- 0.2 nm, mainly along the superhelical axis). An even higher rigidity was found for relative motions (distance histone tails for more than 20 ns. Main purpose of the fluctuations) of segments seperated by half a superhelical turn (approximately +/- 0.1 nm). The N-terminal tails underwent dramatic conformational rearrngements on the nanosecond time scale toward partially and transiently wrapped states around the DNA many of the histone tail changes corresponded to coupled association and folding events from fully solvent-exposed states toward complexes with the major and minor grooves of DNA. The simulations indicate that the rapid conformational changes of the tails can modulate the DNA accessibility within a few nanoseconds. (c) 2007 Wiley Periodicals, Inc.