title: Exposing the co-adaptive potential of protein-protein interfaces through computational sequence design.
abstract: BACKGROUND
  In nature, protein-protein interactions are constantly evolving under various selective pressures. Nonetheless, it is expected that crucial interactions are maintained through compensatory mutations between interacting proteins. Thus, many studies have used evolutionary sequence data to extract such occurrences of correlated mutation. However, this research is confounded by other evolutionary pressures that contribute to sequence covariance, such as common ancestry.
  
  
  RESULTS
  Here, we focus exclusively on the compensatory mutations deriving from physical protein interactions, by performing large-scale computational mutagenesis experiments for >260 protein-protein interfaces. We investigate the potential for co-adaptability present in protein pairs that are always found together in nature (obligate) and those that are occasionally in complex (transient). By modeling each complex both in bound and unbound forms, we find that naturally transient complexes possess greater relative capacity for correlated mutation than obligate complexes, even when differences in interface size are taken into account.
authors.affiliation: School of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Menachem
authors.initials: M
authors.lastname: Fromer
authors.forename: Michal
authors.initials: M
authors.lastname: Linial
mesh_terms: D000220:Adaptation, Biological; D001483:Base Sequence; D019295:Computational Biology; D019143:Evolution, Molecular; D009154:Mutation; D011485:Protein Binding / Q000235:genetics; D011506:Proteins / Q000737:chemistry* / Q000235:genetics
chemical_list: D011506:Proteins