A Searchable Database for Comparing Protein−Ligand Binding Sites for the Analysis of Structure−Function Relationships

The rapid expansion of structural information for protein−ligand binding sites is potentially an important source of information in structure-based drug design and in understanding ligand cross reactivity and toxicity. We have developed a large database of ligand binding sites extracted automatically from the Protein Data Bank. This has been combined with a method for calculating binding site similarity based on geometric hashing to create a relational database for the retrieval of site similarity and binding site superposition. It contains an all-against-all comparison of binding sites and holds known protein−ligand binding sites, which are made accessible to data mining. Here we demonstrate its utility in two structure-based applications: in determining site similarity and in aiding the derivation of a receptor-based pharmacophore model. The database is available from http://www.bioinformatics.leeds.ac.uk/sb/.