**************OWARI COMPLEX SEMINAR LXXIX**************

Title:Docking study of epigenetic enzymes and its inhibitor

Speaker:Dr. MISHIMA Hirokazu

Affiliation:Theoretical Biophysics Laboratory, Department of Physics, Graduate School of Science, Nagoya University

Date:Aug. 6th (Tue.), 13:30 (About two hours)

Place:Lecture room 2 (1F), Graduate School of Informatics

Abstract:Epigenetics is an area of biological study which covers processes during which a constant DNA sequence can produce variable gene expression patterns. An important molecular process of epigenetics which controls variable gene expressions is a histone modification. Histones form into an octamer with a barrel shape. The histone octamer stores DNA and silences gene expressions by wrapping DNA around itself tightly. 
Some residues of histone can be modified chemically. Chemical modifications of histone residues unwrap DNA and activate gene expressions. The processes of modifications are reversible and those are controlled by counter active enzymes. It has been known experimentally that the enzymes can cause serious diseases. Therefore, inhibitors of the enzymes are being developed as drugs of those diseases. The target of this study is one of the developed inhibitor. This inhibitor act on two kinds of highly homologous enzymes but it affects one of them with kinetic selectivity. An exploration of structural space based on a molecular dynamics simulation is expected to elucidate the mechanism of the selectivity. I will show attempts of an elucidation of the mechanism of the selectivity using a replica exchange umbrella sampling MD simulation.

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