Current computational methods for the prediction of function from structure are restricted to the detection of similarities and subsequent transfer of functional annotation. In a significant minority of cases, global sequence or structural (fold) similarities do not provide clues about protein function. In these cases, one alternative is to detect local binding site similarities. These may still reflect more distant evolutionary relationships as well as unique physico-chemical constraints necessary for binding similar ligands, thus helping pinpoint the function. In the present work, we ask the following question: is it possible to discriminate within a dataset of non-homologous proteins those that bind similar ligands based on their binding site similarities?