Homology modeling of Suv39h1 and discovery of its small molecule inhibitors by virtual screening and their in vitro validation

• Author / Creator

  Hosamani, Ishwar V

• Epigenetic modifications are carried out by specific enzymes and are reversible making them a viable and attractive target to design inhibitors to reset the epigenetic regulatory machinery of the cell and restore it to its normal state. Suppressor of variegation 3-9 homolog 1 (Suv39h1) is a histone 3 lysine 9 (H3K9) trimethylase that plays an important role in heterochromatin formation, mitosis, and its misregulation has been implicated in several types of cancer. In this thesis, a homology model of human Suv39h1 was constructed, optimized and validated and used for virtual screening against several small molecule databases to find its potential small molecule inhibitors. The binding sites of three ligands i.e. S-Adenosyl Methionine, Chaetocin and N-terminal of H3K9 peptide, on the homology model of Suv39h1 were determined and used for virtual screening. The small molecules predicted to bind to Suv39h1 with high affinity were tested by an in vitro assay.

• Subjects / Keywords

  • Methyltransferases
  • SUV39h1
  • Histones
  • Homology modeling
  • Epigenetics
  • Virtual screening

• Graduation date

  Fall 2013

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/R3Q23R77T

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.