SUMMARY: Herein, we present COCOMAPS 2.0, for the analysis, visualization, and comparison of the interface in protein-protein and protein-nucleic acid complexes. COCOMAPS 2.0 complements the residue-level and buried surface area analyses of the original COCOMAPS tool with a comprehensive and accurate atomic-level characterization of the interface, enabling detailed interpretation of molecular recognition. Furthermore, it provides a greatly enhanced flexibility, interactivity, and efficiency in graphical visualizations. AVAILABILITY AND IMPLEMENTATION: COCOMAPS 2.0 is accessible as a public web tool at https://aocdweb.com/BioTools/cocomaps2 and as a standalone code at https://doi.org/10.5281/zenodo.17390665.

BACKGROUND: Properly scoring protein-protein docking models to single out the correct ones is an open challenge, also object of assessment in CAPRI (Critical Assessment of PRedicted Interactions), a community-wide blind docking experiment. We introduced in the field CONSRANK (CONSensus RANKing), the first pure consensus method. Also available as a web server, CONSRANK ranks docking models in an ensemble based on their ability to match the most frequent inter-residue contacts in it. We have been blindly testing CONSRANK in all the latest CAPRI rounds, where we showed it to perform competitively with the state-of-the-art energy and knowledge-based scoring functions. More recently, we developed Clust-CONSRANK, an algorithm introducing a contact-based clustering of the models as a preliminary step of the CONSRANK scoring process. In the latest CASP13-CAPRI joint experiment, we participated as scorers with a novel pipeline, combining both our scoring tools, CONSRANK and Clust-CONSRANK, with our interface analysis tool COCOMAPS. Selection of the 10 models for submission was guided by the strength of the emerging consensus, and their final ranking was assisted by results of the interface analysis. RESULTS: As a result of the above approach, we were by far the first scorer in the CASP13-CAPRI top-1 ranking, having high/medium quality models ranked at the top-1 position for the majority of targets (11 out of the total 19). We were also the first scorer in the top-10 ranking, on a par with another group, and the second scorer in the top-5 ranking. Further, we topped the ranking relative to the prediction of binding interfaces, among all the scorers and predictors. Using the CASP13-CAPRI targets as case studies, we illustrate here in detail the approach we adopted. CONCLUSIONS: Introducing some flexibility in the final model selection and ranking, as well as differentiating the adopted scoring approach depending on the targets were the key assets for our highly successful performance, as compared to previous CAPRI rounds. The approach we propose is entirely based on methods made available to the community and could thus be reproduced by any user.

SUMMARY: Herein, we present CONSRANK, a web tool for analyzing, comparing and ranking protein-protein and protein-nucleic acid docking models, based on the conservation of inter-residue contacts and its visualization in 2D and 3D interactive contact maps. AVAILABILITY AND IMPLEMENTATION: CONSRANK is accessible as a public web tool at https://www.molnac.unisa.it/BioTools/consrank/. CONTACT: [email protected].

BACKGROUND: Molecular Dynamics (MD) simulations of protein complexes suffer from the lack of specific tools in the analysis step. Analyses of MD trajectories of protein complexes indeed generally rely on classical measures, such as the RMSD, RMSF and gyration radius, conceived and developed for single macromolecules. As a matter of fact, instead, researchers engaged in simulating the dynamics of a protein complex are mainly interested in characterizing the conservation/variation of its biological interface. RESULTS: On these bases, herein we propose a novel approach to the analysis of MD trajectories or other conformational ensembles of protein complexes, MDcons, which uses the conservation of inter-residue contacts at the interface as a measure of the similarity between different snapshots. A "consensus contact map" is also provided, where the conservation of the different contacts is drawn in a grey scale. Finally, the interface area of the complex is monitored during the simulations. To show its utility, we used this novel approach to study two protein-protein complexes with interfaces of comparable size and both dominated by hydrophilic interactions, but having binding affinities at the extremes of the experimental range. MDcons is demonstrated to be extremely useful to analyse the MD trajectories of the investigated complexes, adding important insight into the dynamic behavior of their biological interface. CONCLUSIONS: MDcons specifically allows the user to highlight and characterize the dynamics of the interface in protein complexes and can thus be used as a complementary tool for the analysis of MD simulations of both experimental and predicted structures of protein complexes.

BACKGROUND: The development of accurate protein-protein docking programs is making this kind of simulations an effective tool to predict the 3D structure and the surface of interaction between the molecular partners in macromolecular complexes. However, correctly scoring multiple docking solutions is still an open problem. As a consequence, the accurate and tedious screening of many docking models is usually required in the analysis step. METHODS: All the programs under CONS-COCOMAPS have been written in python, taking advantage of python libraries such as SciPy and Matplotlib. CONS-COCOMAPS is freely available as a web tool at the URL:http://www.molnac.unisa.it/BioTools/conscocomaps/. RESULTS: Here we presented CONS-COCOMAPS, a novel tool to easily measure and visualize the consensus in multiple docking solutions. CONS-COCOMAPS uses the conservation of inter-residue contacts as an estimate of the similarity between different docking solutions. To visualize the conservation, CONS-COCOMAPS uses intermolecular contact maps. CONCLUSIONS: The application of CONS-COCOMAPS to test-cases taken from recent CAPRI rounds has shown that it is very efficient in highlighting even a very weak consensus that often is biologically meaningful.

SUMMARY: Herein we present COCOMAPS, a novel tool for analyzing, visualizing and comparing the interface in protein-protein and protein-nucleic acids complexes. COCOMAPS combines traditional analyses and 3D visualization of the interface with the effectiveness of intermolecular contact maps. AVAILABILITY: COCOMAPS is accessible as a public web tool at http://www.molnac.unisa.it/BioTools/cocomaps CONTACT: [email protected]; [email protected].

UNLABELLED: The increasing number of available atomic 3D structures of transmembrane channel proteins represents a valuable resource for better understanding their structure-function relationships and to eventually predict their selectivity. Herein, we present PoreLogo, an automatic tool for analysing, visualizing and comparing the amino acid composition of transmembrane channels and its conservation across the corresponding protein family. AVAILABILITY: PoreLogo is accessible as a public web server at http://www.ebi.ac.uk/thornton-srv/software/PoreLogo/.