In the cell nucleus, DNA wraps around histone proteins, forming nucleosome particles, and packs into a highly negatively charged structure, the chromatin. The linker histone is a protein that binds to the nucleosome and determines how the nucleosomes are linked to each other. To simulate the nucleosome-linker histone interactions, we applied a Brownian Dynamics (BD) technique together with normal mode analysis (NMA). NMA of the nucleosome revealed the most prominent modes of motion of its two linker DNAs. The results were used to generate conformations of the linker DNAs which were used in BD simulations of docking of a linker histone and its mutants to the nucleosome. From the simulations, two distinct binding sites on the linker histone were identified. The residues found to be most important for binding in the simulations with the linker histone mutants are consistent with experimental data. Moreover, a unique binding mode of the linker histone to the nucleosome was found for a wide range of conformations of the linker DNAs. As well as providing insights into the determinants of linker histone-nucleosome binding, the results are valuable for higher-order modelling of the chromatin.View Large Image | View Hi-Res Image | Download PowerPoint Slide