ProteinsPlus: interactive analysis of protein-ligand binding interfaces.

Due to the increasing amount of publicly available protein structures searching, enriching and investigating these data still poses a challenging task. The ProteinsPlus web service (https://proteins.plus) offers a broad range of tools addressing these challenges. The web interface to the tool collection focusing on protein-ligand interactions has been geared towards easy and intuitive access to a large variety of functionality for life scientists. Since our last publication, the ProteinsPlus web service has been extended by additional services as well as it has undergone substantial infrastructural improvements. A keyword search functionality was added on the start page of ProteinsPlus enabling users to work on structures without knowing their PDB code. The tool collection has been augmented by three tools: StructureProfiler validates ligands and active sites using selection criteria of well-established protein-ligand benchmark data sets, WarPP places water molecules in the ligand binding sites of a protein, and METALizer calculates, predicts and scores coordination geometries of metal ions based on surrounding complex atoms. Additionally, all tools provided by ProteinsPlus are available through a REST service enabling the automated integration in structure processing and modeling pipelines.

StructureProfiler: an all-in-one tool for 3D protein structure profiling.

MOTIVATION: Three-dimensional protein structures are important starting points for elucidating protein function and applications like drug design. Computational methods in this area rely on high quality validation datasets which are usually manually assembled. Due to the increase in published structures as well as the increasing demand for specially tailored validation datasets, automatic procedures should be adopted. RESULTS: StructureProfiler is a new tool for automatic, objective and customizable profiling of X-ray protein structures based on the most frequently applied selection criteria currently in use to assemble benchmark datasets. As examples, four dataset configurations (Astex, Iridium, Platinum, combined), all results of the combined tests and the list of all PDB Ids passing the combined criteria set are attached in the Supplementary Material. AVAILABILITY AND IMPLEMENTATION: StructureProfiler is available as part of the ProteinsPlus web service http://proteins.plus and as standalone tool in the NAOMI ChemBio Suite. Dataset updates together with the tool can be found on http://www.zbh.uni-hamburg.de/structureprofiler. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

From cheminformatics to structure-based design: Web services and desktop applications based on the NAOMI library.

Nowadays, computational approaches are an integral part of life science research. Problems related to interpretation of experimental results, data analysis, or visualization tasks highly benefit from the achievements of the digital era. Simulation methods facilitate predictions of physicochemical properties and can assist in understanding macromolecular phenomena. Here, we will give an overview of the methods developed in our group that aim at supporting researchers from all life science areas. Based on state-of-the-art approaches from structural bioinformatics and cheminformatics, we provide software covering a wide range of research questions. Our all-in-one web service platform ProteinsPlus (http://proteins.plus) offers solutions for pocket and druggability prediction, hydrogen placement, structure quality assessment, ensemble generation, protein-protein interaction classification, and 2D-interaction visualization. Additionally, we provide a software package that contains tools targeting cheminformatics problems like file format conversion, molecule data set processing, SMARTS editing, fragment space enumeration, and ligand-based virtual screening. Furthermore, it also includes structural bioinformatics solutions for inverse screening, binding site alignment, and searching interaction patterns across structure libraries. The software package is available at http://software.zbh.uni-hamburg.de.

ProteinsPlus: a web portal for structure analysis of macromolecules.

With currently more than 126 000 publicly available structures and an increasing growth rate, the Protein Data Bank constitutes a rich data source for structure-driven research in fields like drug discovery, crop science and biotechnology in general. Typical workflows in these areas involve manifold computational tools for the analysis and prediction of molecular functions. Here, we present the ProteinsPlus web server that offers a unified easy-to-use interface to a broad range of tools for the early phase of structure-based molecular modeling. This includes solutions for commonly required pre-processing tasks like structure quality assessment (EDIA), hydrogen placement (Protoss) and the search for alternative conformations (SIENA). Beyond that, it also addresses frequent problems as the generation of 2D-interaction diagrams (PoseView), protein-protein interface classification (HyPPI) as well as automatic pocket detection and druggablity assessment (DoGSiteScorer). The unified ProteinsPlus interface covering all featured approaches provides various facilities for intuitive input and result visualization, case-specific parameterization and download options for further processing. Moreover, its generalized workflow allows the user a quick familiarization with the different tools. ProteinsPlus also stores the calculated results temporarily for future request and thus facilitates convenient result communication and re-access. The server is freely available at http://proteins.plus.

The Art of Compiling Protein Binding Site Ensembles.

Structure-based drug design starts with the collection, preparation, and initial analysis of protein structures. With more than 115,000 structures publically available in the Protein Data Bank (PDB), fully automated processes reliably performing these important preprocessing steps are needed. Several tools are available for these tasks, however, most of them do not address the special needs of scientists interested in protein-ligand interactions. In this paper, we summarize our research activities towards an automated processing pipeline from raw PDB data towards ready-to-use protein binding site ensembles. Starting from a single protein structure, the pipeline covers the following phases: Extracting structurally related binding sites from the PDB, aligning disconnected binding site sequences, resolving tautomeric forms and protonation, orienting hydrogens and flippable side-chains, structurally aligning the multitude of binding sites, and performing a reasonable reduction of ensemble structures. The pipeline, named SIENA, creates protein-structural ensembles for the analysis of protein flexibility, molecular design efforts like docking or de novo design within seconds. For the first time, we are able to process the whole PDB in order to create a large collection of protein binding site ensembles. SIENA is available as part of the ZBH ProteinsPlus webserver under http://proteinsplus.zbh.uni-hamburg.de.