Moleküler dinamik simülasyonlarıyla histon H3 kuyruğundaki metillenmiş lizin amino asitleri arasındaki istatistiksel korelasyonların belirlenmesi

Post-translational modifications of histone tails have been a very favored topic in Molecular Biology since the proposal of "histone code" hyphothesis. Histone H3 tail is the most well-known one of the histone proteins that undergoes several chemical modifications thus affecting a variety of physiological processes. Moreover, an expanding knowledge of communications between different modifications have emerged in recent years. Although the downstream outcomes of the most of these modifications have been revealed, the detailed mechanism of this dynamic cross-talk between different modifications still remain to be elucidated. In this study, the cooperativity between histone H3 lysine 4 (H3K4) and lysine 9 (H3K9) methylations were aimed to be investigated by Molecular Dynamics (MD) simulations. For this purpose, MD simulations of three types of H3 tails (unmodified H3 tail, tri-methylated K4 (H3K4me3), tri-methylated K9 (H3K9me3)) were carried out. Subsequently, Modal Analysis was performed to the trajectories in order to reveal the distance fluctuation correlations between the residues. By using these residue correlations, statistical mechanical formulations were derived to relate the cooperativity between the methylated residues to the distance fluctuations at residue level. According to the correlation function results, the cross-regulation patterns between the modifications were predicted on statistical thermodynamics basis.