Deciphering the histone code by using molecular dynamics simulations
Abstract
Cellular DNA is tightly packed with histones, proteins directly involved in regulation of gene expression with impact on numerous biological processes including cell differentiation, epigenetics and disease development. In particular, histones achieve this regulation by various types and combinations of post-translational modifications that are interpreted by interactions with specific effector proteins. Despite their pivotal role in different biological contexts, effects of histone modifications on recruitment of effectors at the microscopic level remains elusive. Here, our main goal is to further our understanding of microscopic mechanisms determining the function of histone modifications. To do this, we will use molecular dynamics simulations, a widely used high-resolution computational method for studying biomolecular properties and behavior at the atomistic level. More specifically, we intend to systematically investigate how different histone modifications and combinations thereof affect interactions with related effectors. In addition, histone effectors dedicated to recognition of lysine methylation and acetylation have been recently shown as promising targets for small molecule drugs. To this end, we intend to use molecular dynamics simulations to model interactions of effectors with known active molecules in order to examine binding mechanism as well as explore binding of other compounds by using perturbation free energy calculations.
Schlagworte molecular dynamics simulations post-translational modifications oxidative stress epigenetics
Publikationen
Mitarbeiter*innen
Drazen Petrov
Drazen Petrov Ph.D.
drazen.petrov@boku.ac.at
Tel: +43 1 47654-89415
Projektleiter*in
01.07.2017 - 30.06.2019