A cross-species interacting database inferring from three-dimensional (3D) protein structure complexes and a novel scoring function by using 3D-domain interologs. For a query protein, the 3D-Interologs database utilizes BLAST to identify homologous proteins and the interacting partners from multiple species. Based on the novel scoring function and structure complexes, 3D-Interologs provides the statistic significances, the interacting models (e.g. hydrogen bonds and conserved amino acids), and functional annotations of interacting partners of a query protein. The identification of orthologous proteins of multiple species is able to use to study on protein-protein evolution, protein functions, and cross-referencing of proteins.