CM2D3: Furnishing the Human Interactome with Structural Models of Protein Complexes Derived by Comparative Modeling and Docking.

The human interactome is composed of around half a million interactions according to recent estimations and it is only for a small fraction of those that three-dimensional structural information is available. Indeed, the structural coverage of the human interactome is very low and given the complexity and time-consuming requirements of solving protein structures this problem will remain for the foreseeable future. Structural models, or predictions, of protein complexes can provide valuable information when the experimentally determined 3D structures are not available. Here we present CM2D3, a relational database containing structural models of the whole human interactome derived both from comparative modeling and data-driven docking. Starting from a consensus interactome derived from integrating several interactomics databases, a strategy was devised to derive structural models by computational means. Currently, CM2D3 includes 33338 structural models of which 5121 derived from comparative modeling and the remaining from docking. Of the latter, the structures of 14554 complexes were derived from monomers modeled by M4T while the rest were modeled with structures as predicted by AlphaFold2. Lastly, CM2D3 complements existing resources by focusing on models derived from both free-docking, as opposed to template-based docking, and hence expanding the available structural information on protein complexes to the scientific community. Database URL:http://www.bioinsilico.org/CM2D3.

Galaxy InteractoMIX: An Integrated Computational Platform for the Study of Protein-Protein Interaction Data.

Protein interactions play a crucial role among the different functions of a cell and are central to our understanding of cellular processes both in health and disease. Here we present Galaxy InteractoMIX (http://galaxy.interactomix.com), a platform composed of 13 different computational tools each addressing specific aspects of the study of protein-protein interactions, ranging from large-scale cross-species protein-wide interactomes to atomic resolution level of protein complexes. Galaxy InteractoMIX provides an intuitive interface where users can retrieve consolidated interactomics data distributed across several databases or uncover links between diseases and genes by analyzing the interactomes underlying these diseases. The platform makes possible large-scale prediction and curation protein interactions using the conservation of motifs, interology, or presence or absence of key sequence signatures. The range of structure-based tools includes modeling and analysis of protein complexes, delineation of interfaces and the modeling of peptides acting as inhibitors of protein-protein interactions. Galaxy InteractoMIX includes a range of ready-to-use workflows to run complex analyses requiring minimal intervention by users. The potential range of applications of the platform covers different aspects of life science, biomedicine, biotechnology and drug discovery where protein associations are studied.