Merging the ligand core with a new R-group requires that both the linking atom on the template core and on the attachable R-group are specified. The merging is carried out with the RDKit editable molecule. RDKit is further used to generate 3D conformers using the ETKDG method. The generated conformers are aligned, and energy minimised using distance constraints to the common core (identified by a maximum common structure search). In this way, we can enforce the conformations of the generated molecules to only vary from the core in the region of the added R-group. This region may additionally be extended by adding further atoms into the "flexible substructure" of the template. For convenience, we provide a minimal set of around 500 R-groups that are commonly used in medicinal chemistry optimisation. R-groups can be interactively selected from the library using the mols2grid package, or the user may prepare their own molecules for attachment (see Tutorial).