Protein interaction networks revealed by proteome coevolution

• DOI: 10.1126/science.aaw6718
• Publication Date: 2021-11-05T21:25:55Z
• Authors: Qian Cong; Ivan Anishchenko; Sergey Ovchinnikov; David Baker
• Keywords: Biological Coevolution; Bacterial Proteins; Proteome; Protein Conformation; Escherichia coli Proteins; Escherichia coli; Mycobacterium tuberculosis; Protein Interaction Maps; 3. Good health

Predicting protein pairs

Biological function is driven by interaction between proteins. High-throughput experimental techniques have provided large datasets of protein interactions in several organisms; however, much combinatorial space remains uncharted. Cong et al. predict protein interfaces by identifying coevolving residues in aligned protein sequences (see the Perspective by Vajda and Emili). In comparison with gold-standard and negative control sets, they show that the accuracy is higher than for proteome-wide two-hybrid and mass spectrometry screens. The approach predicts 1618 protein interactions in Escherichia coli , 682 of which were unanticipated, and 911 interacting pairs in Mycobacterium tuberculosis , most of which had not been previously described. With an expected false-positive rate of between 10 and 20%, the predicted interactions and networks provide an excellent starting point for further study.

Science , this issue p. 185 ; see also p. 120