Structure-Function Relationships in Protein Complexes

Abstract

Structural and functional characterization of protein-protein interactions is important for understanding molecular mechanisms in a living cell. Structure-function relationships are usually studied for individual proteins. We present a quantitative analysis of structure-function relationships for proteins and protein-protein complexes, based on 4950 protein-protein structures from the DOCKGROUND resource (http://dockground.compbio.ku.edu). Structural similarity of individual proteins, protein complexes, and protein-protein interfaces was quantified by TM-score. Functional similarity was represented by GO-score, which quantifies similarity between two sets of Gene Ontology (GO) terms (we used only the molecular function domain of the GO annotation). The GO-scores were calculated for the individual proteins and the protein complexes separately, based on the complete sets of GO terms, and on the GO terms related to the function of the complex only. The results showed only a weak correlation of structural and functional similarity in protein complexes. Proteins and their interfaces were further clustered based on the structural and functional similarity, and the functional/structural variability of the clusters was analyzed. The function of structurally similar interfaces was determined to be more variable than that of the structurally similar full proteins.