creator Kohestani, Havva 2019 Summer 2019 Thesis Illinois Institute of Technology PHYS / Physics advisor Wereszczynski, Jeff Biophysics Molecular biology Molecular physics DNA-Protein Interaction DNA Unwrapping H2A.B Histone Variant Molecular Dynamics Nucleosome Radius of Gyration en The H2A.B histone is a highly evolving vertebrate specific variant of the H2A histone family. It has been implicated in increased gene expression, and experiments have shown that incorporation of H2A.B into nucleosomes results in more extended structures with fewer wrapped DNA base pairs. To study the molecular mechanisms of H2A.B, we have performed a series of conventional and enhanced sampling molecular dynamics simulation of H2A.B and canonical H2A containing nucleosomes.Results of adaptively biased molecular simulations show that substitution of canonical H2A with H2A.B results in geometrical changes such as unwrapping of 10 to 15 base pairs of DNA on each side of the nucleosome and an increase in the diameter and radius of gyration, which is in agreement with previous AFM, FRET, and SAXS experiments. DNA unwinding is energetically favorable in H2A.B containing compared to canonical nucleosomes, while in both systems we observe a wide range of sampling over various structures of DNA. H3 histone tails excluded simulations, show the importance and effect of N-terminal residues of H3 histones on attachment of DNA at the entry/exit sites to nucleosome protein core. Clustering and hydrogen bond analysis suggest that introduction of H2A.B to nucleosome systems triggers mechanisms leading to rearrangement of hydrogen bond network which may influence the pattern and intensity of interactions between DNA-protein and protein-protein complexes. born digital application/pdf In Copyright http://rightsstatements.org/page/InC/1.0/ Restricted Access http://hdl.handle.net/10560/islandora:1000778