In WP4 we simulate individual nucleosomes, chromatin fibers and whole chromosomes as well as cell nuclei using parallel and grid super-computers with ~10.000 CPUs. The impact of different nucleosomal positions and epigenetic modifications on the nucleosomal structure and the chromatin fiber conformation will be assessed by novel Monte Carlo approaches. To understand the higher-order architecture Brownian Dynamics simulations of entire cell nuclei with molecular resolution, morphogenic processes and transcriptional states will be made. This will result in a virtual multi-scale model with unprecedented spatial and temporal resolution to provide novel insights into genome organization. Importantly, all the resulting virtual genome architectures will be based and compared to experiment and will be used to prompt again experiments and vice versa in a reiterative cycle.
T. A. Knoch, Approaching the three-dimensional organization of the human genome: structural-, scaling- and dynamic-properties in the simulation of interphase chromosomes and cell nuclei long–range correlations in complete genomes, in vivo analysis of the chromatin distribution construct conversions in simultaneous co–transfections. Ruperto Carola University, Heidelberg, Germany, and TAK-Press, Dr. Tobias A. Knoch, Mannheim, Germany, ISBN 3-00-009960-3 (hard cover), ISBN 3-00-009959-X (soft cover), ISBN 3-00-035856-0 (DVD), 2002.
Kepper, N., Ettig, R., Stehr, R., Wedemann, G. & Rippe, K. (2011). Force spectroscopy of chromatin fibers: extracting energetics and structural information from Monte Carlo simulations, Biopolymers, 95(7), 435–447.
Stehr, R., Kepper, N., Rippe, K. and Wedeman, G. (2008). The effect of the internucleosomal interaction potential on the folding of the chromatin fiber. Biophys. J. 95, 3677–3691.
Kepper, N., Foethke, D., Stehr, R., Wedeman, G. and Rippe, K. (2008). Nucleosome geometry and internucleosomal interactions control the chromatin fiber conformation, Biophys. J. 95, 3692–3705.