Link to bioRxiv paper:

http://biorxiv.org/cgi/content/short/2020.10.17.343962v1?rss=1

Authors: Gong, W., Guerler, A., Zhang, C., Warner, E., Li, C., Zhang, Y.

Abstract:

Genome-wide protein-protein interaction determination (or interactome) remains a significantly unsolved problem in structural biology. The difficulty is twofold since high-throughput experiments (THEs) have often high false-positive rate in assigning PPIs and PPI quaternary structure is much more difficult to solve than tertiary structure using traditional structural biology techniques. We proposed a uniform pipeline to address both difficulties which recognizes PPIs by combining multi-chain threading with high-throughput experimental (HTE) data through naive Bayesian classifiers, where quaternary structures are then constructed by mapping monomer models with the dimeric frameworks through interface-specific structural alignments. The pipeline was applied to the Escherichia coli genome and created 35,125 confident PPIs that is 4.5-fold higher than HTE alone. Graphic analyses of the PPI networks reveal a scale-free cluster size distribution, which was found critical to the robustness of genome evolution and the centrality of functionally important proteins that are essential to E. coli survival. Finally, high-confidence complex structure models were constructed for all predicted PPIs built on quaternary threading templates, which show a close consistency with the experimental structures solved after the modeling. These results demonstrate the significant usefulness of threading-based homologous modeling in both genome-wide PPI network detection and complex structural construction.

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