Figure 1

Usage of the web interface of SuperLigands. From the main menu, the form Compound search can be reached. Here, a PDB ligand can be searched after hetero-ID, name, molecular formula or PDB identifier. In the first column of the results table, two buttons can be found to retrieve more information. The FULL info button delivers detailed information about the selected PDB ligand like molecular formula, atom numbers and occurrence in the PDB. After clicking the DRUGS button, a two-dimensional similarity search among the drugs in the SuperDrug database [16] is performed. The best hits are displayed in a new window. From here, they can be spatially superposed. In the figure, this procedure was carried out for celecoxib, a COX-2 inhibitor which was recently categorised as problematic (see the "Pfizer Statement on New Information Regarding Cardiovascular Safety of Celebrex" [18]). The two-dimensional similarity search in the SuperDrug database delivers only hits below 72% Tanimoto similarity. A following spatial superposition of the best hits reveals a further COX-2 inhibitor, namely valdecoxib, (RMSD 0.26Å and 21 of 22 atoms superposed) as very similar to celecoxib. The Tanimoto similarity of celecoxib and valdecoxib is only 65% and there are two drugs more similar to celecoxib: Sulfaphenazole (71% Tanimoto similarity, spatial superposition with 0.65Å RMSD and 15 of 22 atoms superposed) and Sulfamazone (67% Tanimoto similarity, spatial superposition with 0.32Å RMSD and 17 of 26 atoms superposed). Nevertheless, the three-dimensional comparison here proves to be very important to reveal molecular similarities in addition to topological comparison (as also shown in the example in the section Utility), which is confirmed by the fact that valdecoxib was categorised as toxic [19] and sales of this drug were suspended recently [20].