SUMMARY: The searching of user-defined 3D queries in molecular interfaces is a computationally challenging problem that is not satisfactorily solved so far. Most of the few existing tools focused on that purpose are desktop based and not openly available. Besides that, they show a lack of query versatility, search efficiency and user-friendliness. We address this issue with GeoMine, a publicly available web application that provides textual, numerical and geometrical search functionality for protein-ligand binding sites derived from structural data contained in the Protein Data Bank (PDB). The query generation is supported by a 3D representation of a start structure that provides interactively selectable elements like atoms, bonds and interactions. GeoMine gives full control over geometric variability in the query while performing a deterministic, precise search. Reasonably selective queries are processed on the entire set of protein-ligand complexes in the PDB within a few minutes. GeoMine offers an interactive and iterative search process of successive result analyses and query adaptations. From the numerous potential applications, we picked two from the field of side-effect analyze showcasing the usefulness of GeoMine. AVAILABILITY AND IMPLEMENTATION: GeoMine is part of the ProteinsPlus web application suite and freely available at https://proteins.plus. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

MOTIVATION: In this paper a new algorithmic approach is presented, which automatically generates structure diagrams of molecular complexes. A complex diagram contains the ligand, the amino acids of the protein interacting with the ligand and the hydrophilic interactions schematized as dashed lines between the corresponding atoms. The algorithm is based on a combinatorial optimization strategy which solves parts of the layout problem non-heuristically. The depicted molecules are represented as structure diagrams according to the chemical nomenclature. Due to the frequent usage of complex diagrams in the scientific literature as well as in text books dealing with structural biology, biochemistry and medicinal chemistry, the new algorithm is a key element for computer applications in these areas. RESULTS: The method was implemented in the new software tool PoseView. It was tested on a representative dataset containing 305 protein-ligand complexes in total from the Brookhaven Protein Data Bank. PoseView was able to find collision-free layouts for more than three quarters of all complexes. In the following the layout generation algorithm is presented and, additional to the statistical results, representative test cases demonstrating the challenges of the layout generation will be discussed. AVAILABILITY: The method is available as a webservice at http://www.zbh.uni-hamburg.de/poseview.