Homology modeling of parasite histone deacetylases to guide the structure-based design of selective inhibitors

J Mol Graph Model. 2015 Nov:62:342-361. doi: 10.1016/j.jmgm.2015.10.006. Epub 2015 Oct 19.


Histone deacetylases (HDACs) are promising epigenetic targets for the treatment of various diseases, including cancer and neurodegenerative disorders. There is evidence that they can also be addressed to treat parasitic infections. Recently, the first X-ray structure of a parasite HDAC was published, Schistosoma mansoni HDAC8, giving structural insights into its inhibition. However, most of the targets from parasites of interest still lack this structural information. Therefore, we prepared homology models of relevant parasitic HDACs and compared them to human and S. mansoni HDACs. The information about known S. mansoni HDAC8 inhibitors and compounds that affect the growth of Trypanosoma, Leishmania and Plasmodium species was used to validate the models by docking and molecular dynamics studies. Our results provide analysis of structural features of parasitic HDACs and should be helpful for selecting promising candidates for biological testing and for structure-based optimisation of parasite-specific inhibitors.

Keywords: Epigenetics; Histone deacetylases; Homology modeling; Molecular docking; Molecular modeling; Parasitic diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiparasitic Agents / chemistry*
  • Catalytic Domain
  • Helminth Proteins / chemistry*
  • Histone Deacetylase Inhibitors / chemistry*
  • Histone Deacetylases / chemistry*
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • Plasmodium falciparum / enzymology
  • Protein Binding
  • Protein Structure, Secondary
  • Protozoan Proteins / chemistry*
  • Schistosoma mansoni / enzymology
  • Zinc / chemistry


  • Antiparasitic Agents
  • Helminth Proteins
  • Histone Deacetylase Inhibitors
  • Protozoan Proteins
  • Histone Deacetylases
  • Zinc