ProteinsPlus: interactive analysis of protein-ligand binding interfaces

Abstract

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.

Figure 1.

The ProteinsPlus GUI. The 3D representation of human deoxy hemoglobin (Hb) complexed with RSR-13 (PDB code: 1G9V (41)) is shown on the left hand side together with the control panel for the NGL viewer options. The central panel contains a scrollable list of structure diagrams of all ligands contained in the PDB file. On the tool panel on the right hand side, the calculation results of WarPP are shown in a table. In the NGL viewer, a water molecule corresponding to one line in the table is shown. The red translucent sphere shows the position of the closest X-ray water molecule and the pink sphere denotes a good average hydrogen bond quality for this water molecule.

Figure 2.

Visualization of METALizer results for Atrolysin C with Batimastat (PDB code: 1DTH (42)). The connection between the coordinating atoms and the metal ion are denoted by solid lines, the optimal geometry is denoted as arrows outgoing from the ion. METALizer predicts three different coordination geometries for the zinc ion bound to chain A of the protein: (A) tetrahedral (Free Sites: 0, Geometry RMSD: 0.190, Overlap Penalty: 0.0, Score: 9.51), (B) trigonal bipyramid (Free Sites: 1, Geometry RMSD: 0.173, Overlap Penalty: 0.0, Score: 12.63) and (C) trigonal prismatic (Free Sites: 2, Geometry RMSD: 0.246, Overlap Penalty: 0.001, Score: 20.29). The tetrahedral geometry is considered to be the best one due to the lowest calculated score.