|IsoCleft Finder is a web-based tool for the detection of local structural and chemical similarities between potential smallmolecule binding cavities and a non-redundant dataset of known small-molecule binding-sites. The dataset, available for download, is composed of 7339 entries representing unique Pfam/PDB-ligand (hetero group code) combinations with known levels of cognateligand similarity.
The query cavity can be uploaded by the user or detected automatically by the system using existing PDB entries or user-provided structures in PDB format. In either case, the user can refine the definition of the cavity interactively via a Jmol interface. Furthermore, users can restrict the search to a subset of the dataset using a cognate-similarity threshold.
Local structural similarities are detected using the IsoCleft software and ranked according to two criteria (number of atoms in common and Tanimoto score of local structural similarity) and the associated statistical significance measures of z-score and p-value. The results, including predicted ligands, target proteins, similarity scores, atoms in common, etc., are shown in a powerful interactive graphical interface. This interface permits the visualisation of target ligands superimposed on the query cavity and additionally provides a table of pairwise targetligand similarities.
IsoCleft Finder is at the moment being hosted at the European Bioinformatics Institute.
Above: IsoCleft example. PDB 1O41 (green) and 1O47 (red). These two structures represent SH2 protein crystalized with RU78300 and RU82209 respectively. Isocleft Identified 31 similar atoms positionned in geometrically equivalent position (sphere representation). In this particular case, IsoCleft allows the visualization of the displacement of binding site atoms caused by differential ligand binding.
Rafael Najmanovich, Natalja Kurbatova & Janet Thornton. Detection of 3D atomic similarities and their use in the discrimination of small-molecule protein binding sites. Bioinformatics 24, 105-111
View the article at Bioinformatics website
IsoCleft Finder Interface paper
Natalja Kurbatova, Matthieu Chartier, María Inés Zylber, Rafael Najmanovich (2013). IsoCleft Finder – a web-based tool for the detection and analysis of protein binding-site geometric and chemical similarities. F1000 Research, 2:117
View the article at F1000 Research website