• drug discovery;
  • epigenetics;
  • modeling;
  • molecular recognition;
  • simulations


The abnormal regulation of epigenetic protein families is associated with the onset and progression of various human diseases. However, epigenetic processes remain relatively obscure at the molecular level, thus preventing the rational design of chemical therapeutics. An array of robust computational and modeling approaches can complement experiments to shed light on the complex mechanisms of epigenetic molecular recognition and can guide medicinal chemists in designing selective and potent drug molecules. Herein we present a review of studies focused on epigenetic molecular recognition from a biomolecular modeling viewpoint. Although the known epigenetic targets are numerous, this review focuses on the more limited protein families on which computational modeling has been successfully applied. Therefore, we review three main topics: 1) histone deacetylases, 2) histone demethylases, and 3) histone tail dynamics. A brief review of the biological background and biomedical relevance is presented for each topic, followed by a detailed discussion of the computational studies and their relevance.