title: Molecular principles of human virus protein-protein interactions.
abstract: BACKGROUND
  Viruses, from the human protein-protein interaction network perspective, target hubs, bottlenecks and interconnected nodes enriched in certain biological pathways. However, not much is known about the general characteristic features of the human proteins interacting with viral proteins (referred to as hVIPs) as well as the motifs and domains utilized by human-virus protein-protein interactions (referred to as Hu-Vir PPIs).
  
  
  RESULTS
  Our study has revealed that hVIPs are mostly disordered proteins, whereas viral proteins are mostly ordered proteins. Protein disorder in viral proteins and hVIPs varies from one subcellular location to another. In any given viral-human PPI pair, at least one of the two proteins is structurally disordered suggesting that disorder associated conformational flexibility as one of the characteristic features of virus-host interaction. Further analyses reveal that hVIPs are (i) slowly evolving proteins, (ii) associated with high centrality scores in human-PPI network, (iii) involved in multiple pathways, (iv) enriched in eukaryotic linear motifs (ELMs) associated with protein modification, degradation and regulatory processes, (v) associated with high number of splice variants and (vi) expressed abundantly across multiple tissues. These aforementioned findings suggest that conformational flexibility, spatial diversity, abundance and slow evolution are the characteristic features of the human proteins targeted by viral proteins. Hu-Vir PPIs are mostly mediated via domain-motif interactions (DMIs) where viral proteins employ motifs that mimic host ELMs to bind to domains in human proteins. DMIs are shared among viruses belonging to different families indicating a possible convergent evolution of these motifs to help viruses to adopt common strategies to subvert host cellular pathways.
  
  
  METHODS
  Hu-Vir PPI data, DDI and DMI data for human-virus PPI can be downloaded from http://cdfd.org.in/labpages/computational_biology_datasets.html.
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Laboratory of Computational Biology, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, Telangana, 500001, India and Graduate School, Manipal University, Manipal, 576104, Karnataka, India Laboratory of Computational Biology, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, Telangana, 500001, India and Graduate School, Manipal University, Manipal, 576104, Karnataka, India.
authors.forename: Rachita Ramachandra
authors.initials: RR
authors.lastname: Halehalli
authors.affiliation: Laboratory of Computational Biology, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, Telangana, 500001, India and Graduate School, Manipal University, Manipal, 576104, Karnataka, India.
authors.forename: Hampapathalu Adimurthy
authors.initials: HA
authors.lastname: Nagarajaram
mesh_terms: D001665:Binding Sites; D019295:Computational Biology / Q000379:methods*; D030562:Databases, Protein; D019143:Evolution, Molecular; D053263:Gene Regulatory Networks; D054884:Host-Pathogen Interactions / Q000235:genetics*; D006801:Humans; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs / Q000235:genetics*; D060066:Protein Interaction Maps; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014777:Virus Diseases / Q000235:genetics* / Q000821:virology; D014780:Viruses / Q000378:metabolism*
chemical_list: D011506:Proteins