Exploring the mechanism how AF9 recognizes and binds H3K9ac by molecular dynamics simulations and free energy calculations.
Histone acetylation is a very important regulatory mechanism in gene expression in the chromatin context. A new protein family-YEATS domains have been found as a novel histone acetylation reader, which could specific recognize the histone lysine acetylation. AF9 is an important one in the YEATS family. Focused on the AF9-H3K9ac (K9 acetylation) complex (ALY) (PDB code: 4TMP) and a serials of mutants, MUT (the acetyllsine of H3K9ac was mutated to lysine), F59A, G77A, and D103A, we applied molecular dynamics simulation and molecular mechanics Poisson-Boltzmann (MM-PBSA) free energy calculations to examine the role of AF9 protein in recognition interaction. The simulation results and analysis indicate that some residues of the protein have significant influence on recognition and binding to H3K9ac peptides and hydrophobic surface show the hydrophobic interactions play an important role in the binding. Our work can give important information to understand how the protein AF9 recognizes the peptides H3K9ac. © 2016 Wiley Periodicals, Inc. Biopolymers 105: 779-786, 2016.
Laboratory of Theoretical and Computational Chemistry, Institute of Theoretical Chemistry, Jilin University, Changchun, 130023, People's Republic of China.
Quan
Q
Wang
Laboratory of Theoretical and Computational Chemistry, Institute of Theoretical Chemistry, Jilin University, Changchun, 130023, People's Republic of China.|Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, Changchun, 130023, People's Republic of China.
Qing-Chuan
QC
Zheng
Laboratory of Theoretical and Computational Chemistry, Institute of Theoretical Chemistry, Jilin University, Changchun, 130023, People's Republic of China.|School of Pharmaceutical Sciences, Jilin University, Changchun, 130022, People's Republic of China.
Hong-Xing
HX
Zhang
D006657:Histones / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D056004:Molecular Dynamics Simulation; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding
D006657:Histones; C489901:MLLT3 protein, human; D009687:Nuclear Proteins
H3K9ac peptides; MM/PBSA; histone lysine acetylation; hydrophobic surface; molecular dynamics simulation