SPILLO-PBSS analyzes both empty (in blue) and occupied regions of the protein structure. It takes into account protein flexibility in solution and identifies binding sites even when the protein is not in a conformation suitable for the binding. This video shows a binding site where most of the small molecule is interpenetrated with the atoms of the protein. This result is strongly prohibited (apparently not realistic situation) by the other methods and would have been immediately discarded. The target protein identified through the identification of this binding site has been experimentally validated (for more details, please see the paper at https://pubs.acs.org/doi/10.1021/acs.jmedchem.0c02039%EF%BB%BF ).