Abstract
A novel computational approach of coevolution analysis allowed us to reconstruct the protein-protein interaction network of the Hepatitis C Virus (HCV) at the residue resolution. For the first time, coevolution analysis of an entire viral genome was realized, based on a limited set of protein sequences with high sequence identity within genotypes. The identified coevolving residues constitute highly relevant predictions of protein-protein interactions for further experimental identification of HCV protein complexes. The method can be used to analyse other viral genomes and to predict the associated protein interaction networks.
Highlights
Protein-protein interactions may involve two or more partners
The Blocks In Sequences (BIS) method demonstrated to go beyond the bottleneck of analysis present in current coevolution studies and its improved performance in the present study allows us to realise a complete coevolution analysis of the small Hepatitis C Virus (HCV) genome of 10 proteins, opening the way to coevolution studies of protein-protein interaction networks in viral genomes
BIS2 can be applied on a single protein, on a pair of proteins and on multiple proteins at once as it is the case here for the HCV polyprotein
Summary
Protein-protein interactions may involve two or more partners. The molecular mechanisms underlying these interactions and their implication for the regulation of biological processes might be multiple. BIS2 is a new computationally efficient version of Blocks In Sequences (BIS)[45], a coevolution analysis method that could successfully handle highly conserved proteins such as the Amyloid beta peptide for Alzheimer’s disease and families of very few sequences such as the ATPase protein families These studies highlighted that coevolving protein fragments are indicators of important information explaining folding intermediates, peptide assembly, key mutations with known roles in genetic diseases, distinguished subfamily-dependent motifs[45]. They appear as good starting points for investigating the feasibility of coevolution studies to reconstruct protein-protein networks
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