DNA methyltransferases (DNMTs) are a family of epigenetic enzymes for which inhibition is an attractive strategy for the
treatment of cancer and other diseases. In synergy with experimental approaches, computational methods are increasingly being used to
identify and optimize the activity of inhibitors of DNMTs as well as to rationalize at the molecular level of the mechanism of established
inhibitors. Recently, a crystallographic structure of the methyltransferase domain of human DNMT1 bound to unmethylated DNA was
published encouraging the application of structure-based approaches to design and optimize the activity of currently known inhibitors.
Herein, we review the progress in the discovery and optimization of inhibitors of DNMTs using computational approaches including
homology modeling, docking, pharmacophore modeling, molecular dynamics, and virtual screening.
Keywords: Cancer, docking, drug discovery, enzyme inhibitor, epigenetics, homology modeling, molecular dynamics, natural products,
structure-activity relationships, virtual screening
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Published on: 21 June, 2012
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