Advances in the computational development of DNA methyltransferase inhibitors

DNA methylation is an epigenetic change that results in the addition of a methyl group at the carbon-5 position of cytosine residues. The process is mediated by DNA methyltransferases (DNMTs), a family of enzymes for which inhibition is a promising strategy for the treatment of cancer and other diseases. Here, we review the current status of the computational studies directed to rationalize, at the molecular level, the enzymatic activity of DNMT inhibitors. We also review successful virtual screenings to identify inhibitors with novel scaffolds as well as the emerging efforts to characterize the dynamic behavior of DNMTs. Thus, computational approaches form part of multidisciplinary efforts to further advance epigenetic therapies.