GeoMine: interactive pattern mining of protein–ligand interfaces in the Protein Data Bank

Abstract

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 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. Results 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 analyse showcasing the usefulness of GeoMine. Availability 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.

Binding Site Detection Remastered: Enabling Fast, Robust, and Reliable Binding Site Detection and Descriptor Calculation with DoGSite3

“…An unsuccessful pocket identification is especially obstructive if the druggability of specific binding sites is to be analyzed or the detection method is used to define the dimensions of, e.g., a fragment-bound binding site for molecular docking and fragment growing. The same holds for developing binding site databases for automated pocket comparisons, e.g., with GeoMine. , In these cases, DoGSite3 enables the user to annotate the DoGSite grid based on given reference ligands, ensuring the detection of pockets in the proximity of the reference ligands and allowing for analyses of binding sites that are difficult to detect. If this modification is applied for the druggable binding sites as stored in the scPDB, 99.0% of the binding sites are included with a ligand coverage of at least 80% as compared to 76.4% if this ligand bias option is not enabled.…”

MCDB: A comprehensive curated mitotic catastrophe database for retrieval, protein sequence alignment, and target prediction

“…As previous studies, researchers always focus on such proteins that can form compounds or have structures 55 , 56 , 57 . Fig.…”

“…We usually will focus on such proteins that can form compounds or have structures, since they are very useful for pharmacological and pharmacochemical research 55 , 56 , 57 . Here, we define the ratios for compounds (Ratio_c) and structures (Ratio_s) to help us to show the distribution of these types of proteins in MCDB.…”

ProteinsPlus: a comprehensive collection of web-based molecular modeling tools

“…This requires comprehensive search capabilities. With GeoMine ( 5 , 6 ), we have developed a search engine that allows for the generation of and the search for atom-based geometric query patterns and an extensive textual and numerical filtering of the PDB. The query atoms can be described manually or automatically with varying degrees of detail, from major properties like the corresponding molecule type, i.e.…”