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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
  • Graduation date
    2013-11
  • 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.
  • Language
    English
  • Institution
    University of Alberta
  • Degree level
    Master's
  • Department
    • Department of Oncology
  • Specialization
    • Experimental Oncology
  • Supervisor / co-supervisor and their department(s)
    • Dr. Chan, Gordon (Experimental Oncology)
    • Dr. Tuszynski, Jack (Experimental Oncology)
  • Examining committee members and their departments
    • Dr. Campbell, Robert (Chemistry)
    • Dr. Hendzel, Michael (Experimental Oncology)
    • Dr. Underhill, Alan (Experimental Oncology)