Exploring The Mechanism How AF9 Recognizes H3K9ac By Molecular Dynamics Simulations

In eukaryotic cells,eukaryotic genomes are tightly wound around octamers of core histone proteins to form nucleosomes,the basic unit of chromatin.DNA and histones are structurally stable by electrostatic attraction which caused by the positive charge in the histones and negative charge in the DNA double helix phosphate groups.Usually,histones are very stable,but the outside N-terminals of histones are subject to an enormous number of post-translational modifications(PTM,which including acetylation and methylation of lysine and arginine,phosphorylation of serine and threonine,ubiquitylation and sumoylation of lysine,and other modifications).Those PTM play a fundamental role in regulating chromatin dynamics and the accessibility of the underlying DNA in eukaryotes.As one of the most frequent and representative histone modification,histone lysine acetylation has been well characterized as a mark of active transcription.There are three protein families have been proved as the histone acetyllysine read frame: Bromodomain(BRD);tandem plant homeodomain(PHD)domains and AF9 YEATS domains.Contrast to the BRD and tandem PHD domains,AF9 YEATS adopts an immunoglobin fold and utilizes some aromatic with lysine to form a “sandwiching” like cage to specific recognize the acetyllysine.But,we know little about the molecular mechanism of this phenomenon.In this paper,molecular dynamics(MD)simulations and molecular mechanics/Poisson-Boltzmann surface area(MM-PBSA)approach were employed to explore the interaction between AF9 YEATS and H3K9 ac.In this paper,we mainly focus on four aspect:(1)Characterizing how the AF9 protein binds to H3K9ac;(2)Calculating binding free energies for the AF9-H3K9 ac complexes and other mutants;(3)Elucidating potential amino acid residues involved in interactions with the H3K9ac;(4)ALY and other mutation systems were compared to exploration;(5)Explore the mechanism how YEATS protein family recognize H3K9 ac by studying the protein Taf14;(6)Hydrophobic interactions play an important role in the binding between YEATS protein family and H3K9 ac peptides.