The crystallographic structure of human DNMT1 (PDB ID: 4WXX) was retrieved from the Protein Data Bank (. Missing loops and side-chains were added with YASARA software. The ligands were built and energy-minimized in MOE using the MMFF94x forcefield. The more stable protomers at physiological pH were identified. Molecular docking Molecular Operating Environment (MOE) software was used to generate the dock conformation of protein-ligand complexes. The grid was centered on the carbon atom of the carboxyl group of GLU 1266 (chain A) with a size of 27 Å 3 in the presence of the native ligand (SAM). Using the "Triangle Matcher" method, the binding compounds were subjected to 50 search steps (poses) and the default values for the other parameters. The clusters with an RMSD < 2 Å were visually explored. During the docking simulations, the receptor was considered rigid and the ligands flexible. The conformations with the lowest binding energy were selected for an additional MD analysis.