To begin the calculations with LigBuilder, defining the binding site of the protein of interest is necessary. For this purpose, the software includes the CAVITY module, which analyzes the binding pocket of the protein's three-dimensional (3D) structure of interest . As a result of CAVITY, the required data of the binding pocket is ready for the construction step with the BUILD module (section 2.3.2). The first step was to retrieve DNMT1 3D coordinates from the RCSB Protein Data Bank (PDB). The crystallographic structure of DNMT1 was PDB ID: 4WXX, available online: (accessed on June 30th, 2023) . Chain A from the crystallographic structure of DNMT1, without water molecules, was kept for the calculations, and all water molecules were eliminated. The calculations with CAVITY were in standard ligand mode, with the structure of S-adenosyl-L-homocysteine (SAH) used as a guide for the search of the binding cavities. The cavity with the best druggability prediction was chosen for the de novo design with all the fragment libraries.