Biophysical Society Thematic Meeting| Les Houches 2019

Multiscale Modeling of Chromatin: Bridging Experiment with Theory

Poster Abstracts

15-POS Board 15 ENERGETICS OF UNWRAPPING AND UNSTACKING OF NUCLEOSOMES STUDIED BY ALL-ATOM MOLECULAR DYNAMICS SIMULATIONS Hidetoshi Kono 1 ; Shun Sakuraba 1 ; Hisashi Ishida 1 ; 1 National Institutes for Quantum and Radiological Science and Technology, Molecular Modeling and Simulation Group, Kizugawa, Kyoto, Japan Nucleosomes create the diverse conformations of chromatin by the intra- and inter-nucleosome interactions. The key factors are the unwrapping of DNA and the unstacking of nucleosomes. We investigated the energetics using all-atom molecular dynamics simulations with an enhanced sampling method on a large scale. As for the intra-nucleosomal interaction, free energy for unwrapping the outer superhelical turn of the nucleosomal DNA is about 11.5 kcal/mol, which agrees well with values obtained in single molecule experiments. At one end of the DNA, the first five bps unwrap, after which the next five bps unwrap at the same end with little increase in the free energy. The unwrapping then starts at the other end of the DNA, where 10 bps are unwrapped. At this point, further 15 bps unwrap at either end. The unwrapping of the outer superhelical turn is completed when the other end of the DNA unwraps. A detailed analysis of the free energy profile revealed a variety of conformational states, indicating there are many potential paths to outer superhelical turn unwrapping, but the dominant path is likely to be asymmetric. As for the inter-nucleosomal interaction, the free energy profile for separating two nucleosomes revealed that the H4 histone tails diversify the orientation of the two nucleosomes. The force between the nucleosomes was attractive (about 15 pN per H4 tail), while the force between the nucleosomes was repulsive (about -5 pN) when the H4 tails were not involved in the interaction. The experimental data of the internucleosomal stretching would be the averaged value derived from many different conformations of the nucleosomes, where some nucleosomes have specific H4 tail bridge interactions and others have nonspecific interactions without the H4 tails being involved. These results provide insight into the construction, disruption and repositioning of nucleosomes to understand chromatin dynamics.

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