GeoMine

WarPP predicts the position and orientation of water molecules in small-molecule binding sites. It places and scores water molecules in binding sites of crystallographic structures based on EDIAscorer results and interaction geometries as known from experimentally solved protein structures. WarPP was validated on a high-quality set of 1,500 protein-ligand complexes, containing 20,000 crystallographically observed water molecules. It is sufficiently fast for high-throughput analyses. It correctly places water molecules in approx. 80% of the cases. Users can export the predictions as PDB files for, e.g., molecular docking with JAMDA.

METALizer predicts the coordination geometry of metal ions in metalloproteins. Users can compare potential coordination geometries to those found in the examined structure. The predicted coordination geometries and the observed metal interaction distances can be interactively compared to statistics calculated based on the PDB.

SIENA is a software pipeline enabling the fully automated construction of protein structure ensembles from the PDB. Starting with a single query structure, all binding sites with high sequence similarity are extracted from the PDB, aligned, and superimposed. SIENA also handles complicated cases, such as comparing binding sites at protein domain interfaces or within multimeric proteins.

Three-dimensional protein structures play a vital role in drug design. Structure-based design necessitates an in-depth examination of the available quality data before using the structure in computational experiments and for method evaluation. StructureProfiler assists in automatically profiling sets of protein-ligand complex structures based on multiple quality indicators, ranging from model characteristics, e.g., the R factor, and active site features, e.g., bond length deviations, to ligand properties such as electron density support and the validity of torsion angles.

MicroMiner assists in identifying single-residue substitutions in protein structure databases. It searches protein residue environments with local sequence and structural similarity based on the SIENA methodology. Users can search for structural mutation in the entire PDB, their in-house structure collection, or (subsets of) the AlphaFold Database. They can use the method to explore the mutation landscape of proteins with experimental or predicted structures. MicroMiner can be applied to single domains or even protein-protein or protein-ligand interfaces. Several filter options to simplify downstream analysis are available.

DoGSite3 was developed for predicting robust and reliable small molecule binding sites and computing their geometrical and chemical descriptors. It is based on the grid-based DoGSite algorithm for predicting pockets and their sub-pockets. The new tool is largely rotation- and translation-invariant due to a normalization procedure before binding site prediction. Known ligands in the structure can be used to bias the grid by sufficiently buried ligand fragments. The output encompasses novel chemical binding site descriptors considering solvent accessibility. Compared to its predecessor, it shows increased robustness through comprehensive parameter optimization. DoGSite3 runs finish within seconds.