title: Molecular modeling and virtual screening of DNA methyltransferase inhibitors.
abstract: Inhibition of DNA methyltransferases (DNMTs) is a promising approach for the therapeutic treatment of cancer and other diseases. In this work, we review the recent progress on the molecular modeling and virtual screening toward the identification of key structural features associated with the enzyme inhibitory action of active compounds and to identify DNMT inhibitors with novel molecular scaffolds. We discuss the molecular modeling with the co-factor binding site using a recent crystallographic structure of the methyltransferase domain of human DNMT1. We also review the emerging synergy of molecular modeling and chemoinformatic approaches applied to epigenetic therapies targeting DNMTs.
authors.affiliation: Torrey Pines Institute for Molecular Studies, 11350 SW Village Parkway, Port St. Lucie, Florida 34987, USA. jmedina@tpims.org
authors.forename: José L
authors.initials: JL
authors.lastname: Medina-Franco
authors.forename: Jakyung
authors.initials: J
authors.lastname: Yoo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D019295:Computational Biology; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D008024:Ligands; D015254:DNA Modification Methylases; D004248:DNA (Cytosine-5-)-Methyltransferases