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 timeconsuming 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 (c) 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Automated summary

According to recent estimations, the human interactome consists of around half a million interactions, but only a small fraction of them have available three-dimensional structural information. This study presents CM2D3, a relational database containing structural models of the entire human interactome derived from both comparative modeling and data-driven docking. By using computational methods, structural models were derived from a consensus interactome integrated from multiple interactomics databases. CM2D3 complements existing resources by providing models derived from free-docking, expanding the available structural information on protein complexes.