Masters Degrees (Microbial, Biochemical and Food Biotechnology)

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A combined computational study of the structure and binding of the histone H3 N-terminal domain in the nucleosome
(University of the Free State, 2012-02) Du Preez, Louis Lategan; Patterton, Hugh-George; Hoffman, Matie
English: The histone tails have for decades been regarded as unstructured polypeptide chains which simply served as molecular beacons to protein effectors which modify chromatin. However some experimental evidence shows that the tails may contain structure. Thus we conducted a Molecular Dynamics study of the Histone H3 tail and it’s most important post translationally modified isoforms. The 500 ns experiments showed the evolution of different secondary structure conformations for the different modified isoforms. More interestingly the active isoform showed a statistically significant longer reach compared to the inactive isoform. We next conducted a molecular docking study of the 15 – residue tip of the H3 tail to the nucleosome surface. The starting structures were sampled from the Molecular Dynamics trajectories. The tips showed binding to nucleosome where the H3 tail exits the nucleosome, between the DNA and the octamer. This binding position did not cha nge between the different isoforms. We thus propose a molecular mechanism whereby chromatin compaction is carried out at a nucleosome level, and is regulated by transitions in the N-terminal H3 tail structures, which, in turn, are modulated by specific epigenetic PTM patterns.