Structural Flexibility of the Nucleosome Core Particle at Atomic Resolution Studied by Molecular Dynamics Simulation Danilo Roccatano, Andre Barthel, Martin Zacharias School of Engineering and Science, International University Bremen, Campus Ring 1, D-28759 Bremen, Germany Received 8 November 2006; revised 15 January 2007; accepted 17 January 2007 Published online 24 January 2007 in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/bip.20690 This article was originally published online as an accepted preprint. The ‘‘Published Online’’ date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley. com INTRODUCTION T he nucleosome forms the basic structural unit of the eukaryotic chromatin. The nucleosome core particle consists of 147 base-pairs (bp) of DNA wrapped in a left-handed superhelix 1.65 times around a histone octamer. The octamer is formed by two copies of the histone proteins H2A, H2B, H3, and H4. 1–4 Each nucleo- some is connected to it neighbors by a linker DNA (10–80 bp). Nucleosomes can associate to form compact higher- order fiber structures (diameter of 30 nm) that are essential for the compaction of eukaryotic DNA. 5–9 The nucleosome structure is not static but can change in particular upon ABSTRACT: Comparative explicit solvent molecular dynamics (MD) simulations have been performed on a complete nucleosome core particle with and without N-terminal histone tails for more than 20 ns. Main purpose of the 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 DNA segments separated by one superhelical turn (mean relative displacement of approximately 60.2 nm, mainly along the superhelical axis). An even higher rigidity was found for relative motions (distance fluctuations) of segments separated by half a superhelical turn (approximately 60.1 nm). The N-terminal tails underwent dramatic conformational rearrangements 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. # 2007 Wiley Periodicals, Inc. Biopolymers 85: 407–421, 2007. Keywords: nucleic acid flexibility; nucleosome dynamics; DNA packing; DNA structure and dynamics; histone– DNA interaction; histone tail motion flexibility Structural Flexibility of the Nucleosome Core Particle at Atomic Resolution Studied by Molecular Dynamics Simulation Correspondence to: Martin Zacharias; e-mail: m.zacharias@iu-bremen.de Contract grant sponsor: Pacific Northwest National Laboratories, USA Contract grant number: gc9593 Contract grant sponsor: VolkswagenStiftung Contract grant number: I/80485 This article contains supplementary material available via the Internet at http:// www.interscience.wiley.com/jpages/0006-3525/suppmat V V C 2007 Wiley Periodicals, Inc. Biopolymers Volume 85 / Number 5–6 407