COCaDA-web: an interactive web server for exploratory analysis of interatomic contacts in proteins

Abstract

Protein contacts often serve as prerequisites for characterizing molecular interactions and bonds. Traditional implementations remain computationally expensive, posing significant scalability and usability challenges. We present COCaDA-web, an interactive and user-friendly Web Server that allows users to dynamically explore and visualize protein contact data, building upon the COCaDA (COntact search pruning by C \(\alpha \) Distance Analysis) command-line tool, which is aimed for large-scale protein interatomic contact detection. Users can submit their own queries, or explore precomputed data for over 240,000 proteins in the Protein Data Bank. COCaDA-web includes novel features like pH value customization for protonation-aware analysis and biological assembly support, and takes less than a second to process proteins up to 1000 residues. Detailed results are provided for each entry in a dynamic table, alongside an interactive 3D visualization, annotated PyMOL sessions, and step-by-step usage guides. We demonstrate our tool by performing two comparative analyses of the interatomic contacts of Transthyretin and 5-Hydroxyisourate Hydrolase, two evolutionarily and structurally related proteins yet known to perform distinct biological functions associated with amyloidogenesis and gout. COCaDA-web reveals important differences, especially in their central cavities, that help explain the functional divergence of these proteins. At the moment, the COCaDA-web database contains approximately 746 million contacts, divided into 690 million intra-chain and 55 million inter-chain. COCaDA-web provides a fast, interactive, and scalable platform for protein interatomic contact analysis, combining efficient large-scale contact detection with intuitive visualization and exploration tools. COCaDA-web is freely accessible at https://bioinfo.dcc.ufmg.br/cocada-web , and there are no login requirements.