MOLECULAR DYNAMICS SIMULATION OF HISTONE H3 AND H4 N-TERMINAL TAIL CONFORMATION IN THE PRESENCE AND ABSENCE OF NUCLEOSOME CORE

Abstract

Histone N(C)-terminal tails play an important role in chromatin remodeling and gene regulation. Posttranslational modifications (PTMs) of histone tails are known to be correlated to distinct states of gene activity, but the molecular mechanism of these processes is largely unknown. PTMs alter the electrostatic environment and conformation of histone tails, as well as their interaction with other components. Here we performed extensive Replica Exchange Molecular Dynamics (REMD) simulations for the H4 and H3 tails, isolated and with inclusion of a nucleosome. Our results agree with the predictions of previous theoretical studies for the secondary structure of isolated tails, but show strong dependence on the force field used. In the presence of the nucleosome, the secondary structure of histone tails is destabilized. Furthermore, H4K16 is found to insert into the DNA minor groove, whereas the acetylated H4K16 stays on the surface of DNA.