Inhibitors of DNA Methyltransferases: Insights from Computational Studies

Title:Inhibitors of DNA Methyltransferases: Insights from Computational Studies

Volume: 19 Issue: 21

Author(s): J. Yoo and J. L. Medina-Franco

Affiliation:

Keywords: Cancer, docking, drug discovery, enzyme inhibitor, epigenetics, homology modeling, molecular dynamics, natural products, structure-activity relationships, virtual screening

Abstract: 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.

Cite this article as:

Yoo J. and L. Medina-Franco J., Inhibitors of DNA Methyltransferases: Insights from Computational Studies, Current Medicinal Chemistry 2012; 19 (21) . https://dx.doi.org/10.2174/092986712801323289