Molecular modeling of inhibitors of human DNA methyltransferase with a crystal structure: discovery of a novel DNMT1 inhibitor.

ABSTRACT: DNA methyltransferases (DNMTs) are promising epigenetic targets for the development of novel anticancer drugs and other diseases. Molecular modeling and experimental approaches are being used to identify and develop inhibitors of human DNMTs. Most of the computational efforts conducted so far with DNMT1 employ homology models of the enzyme. Recently, a crystallographic structure of the methyltransferase domain of human DNMT1 bound to unmethylated DNA was published. Following on our previous computational and experimental studies with DNMTs, we herein present molecular dynamics of the crystal structure of human DNMT1. Docking studies of established DNMT1 inhibitors with the crystal structure gave rise to a structure-based pharmacophore model that suggests key interactions of the inhibitors

SUBMITTER: Yoo J 

PROVIDER: S-EPMC3837394 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature