Computational analysis of the binding free energy of H3K9me3 peptide to the tandem tudor domains of JMJD2A

JMJD2A is a histone lysine demethylase enzyme which plays a prominent role in the development of prostate and esophageal squamous cancers. Consisting of a JmjC, a JmjN, two PHD and two tandem tudor domains, JMJD2A recognizes and binds to four different methylated histone peptides: H3K4me3, H4K20me3,...

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Bibliographic Details
Main Authors: Ozboyaci, Musa, Keskin, Ozlem, Erman, Burak, Gursoy, Attila
Format: Conference Proceeding
Language:English
Subjects:
Amino acids
Analytical models
Binding Free Energy
Biochemistry
Cancer
component
Epigenetics
Esophagus
Histone Methylation
Humans
JMJD2A
Molecular Dynamics
Peptides
Power engineering and energy
Proteins
Tail
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Summary:JMJD2A is a histone lysine demethylase enzyme which plays a prominent role in the development of prostate and esophageal squamous cancers. Consisting of a JmjC, a JmjN, two PHD and two tandem tudor domains, JMJD2A recognizes and binds to four different methylated histone peptides: H3K4me3, H4K20me3, H4K20me2 and H3K9me3, via its tudor domains. Of the four histone peptides, only recognition of the H3K4me3 and H4K20me3 by JMJD2A-tudor has been identified. In this study, we investigated the recognition of trimethylated H3K9 by the tandem tudor domains of JMJD2A. Using the molecular dynamics simulations, we performed normal mode and molecular mechanics - Poisson Boltzmann / generalized born - surface area (MM-PB/GB-SA) analysis to find the entropic and enthalpic contributions to binding free energy respectively. We showed that binding of the ligand is mainly driven by favorable van der Waals interactions made after complexation. Our findings suggest that, upon complex formation, H3K9me3 peptide adopts a similar binding mode and the same orientation with H3K4me3 peptide.
DOI:10.1109/HIBIT.2010.5478901