RING 3.0: fast generation of probabilistic residue interaction networks from structural ensembles

Abstract

Residue interaction networks (RINs) are used to represent residue contacts in protein structures. Thanks to the advances in network theory, RINs have been proved effective as an alternative to coordinate data in the analysis of complex systems. The RING server calculates high quality and reliable non-covalent molecular interactions based on geometrical parameters. Here, we present the new RING 3.0 version extending the previous functionality in several ways. The underlying software library has been re-engineered to improve speed by an order of magnitude. RING now also supports the mmCIF format and provides typed interactions for the entire PDB chemical component dictionary, including nucleic acids. Moreover, RING now employs probabilistic graphs, where multiple conformations (e.g. NMR or molecular dynamics ensembles) are mapped as weighted edges, opening up new ways to analyze structural data. The web interface has been expanded to include a simultaneous view of the RIN alongside a structure viewer, with both synchronized and clickable. Contact evolution across models (or time) is displayed as a heatmap and can help in the discovery of correlating interaction patterns. The web server, together with an extensive help and tutorial, is available from URL: https://ring.biocomputingup.it/.

Graphical Abstract

The Residue Interaction Network Generator (RING) web server allows for the calculation of high quality and reliable non-covalent molecular interactions based on geometrical parameters from single and multistate PDB structures.

Figure 1.

Main components of the RING web-server interface. The structure used for the example is an NMR ensemble complex (PDB code: 2LPB) of the mediator coactivator domain 1 of Gal11/med15 (Chain A, green) bound to the central activation domain of Gcn4 (Chain B, orange). (A) Interactive RIN with nodes colored by chain and edges by contact type. (B) Interactive protein structure viewer. Notice that the RIN and structure viewers are connected. Clicking on a residue in one panel will also highlight it in the other. (C) Control panel listing the intra- and inter-chain contacts grouped by type, with two check-boxes to select visualizing intra- and/or inter-chain contacts. Contacts can be filtered out by their frequency in the ensemble (only for multi-state structures) and five different color schemes. (D) Only for multi-state structures: Conformational Dependent Contact Map grouped by contact type. Each point represents at least one contact between a particular residue and any residues in a specific model or molecular dynamic snapshot.

Figure 2.

NMR ensemble complex (PDB code: 2LPB) of the mediator coactivator domain 1 of Gal11/med15 (Chain A, green) bound to the central activation domain of Gcn4 (Chain B, orange). The following panels are shown on the top half: Structural ensemble composed of 13 different conformations (left). Summary of inter-chain contacts with a frequency greater than 50% in all models found by RING (center). Resulting inter-contact network with edges and nodes colored by chain and interaction type (right). The following panels are shown in the bottom half: Key Gcn4 residues interactions that dynamically bind Gal11 in one conformation (left). Range of contact frequency in which these inter-chain interactions are found (center). Resulting inter-contact network highlighting edges and nodes involved in the protein-protein interface (right).