The 5D and 6D approaches were developed in the framework of a large research project on a “virtual laboratory” that can estimate in silico the harmful effects triggered by chemicals (including drugs) and their metabolites, in line with efforts regarding the limitation of animal experimentation [71,750] (https://www.biograf.ch). Most of the QSAR methods just presented only considered the ligands, without any information about the receptor (unless docking is carried out to rene the orientation of the ligand in the receptor-binding pocket). Apart from this exception, these models have an important limitation. Implicitly, the receptor is considered as a unique rigid average structure. This may potentially bias the ligand alignment (when this phase is needed).