title: Towards the prediction of protein interaction partners using physical docking.
abstract: Deciphering the whole network of protein interactions for a given proteome ('interactome') is the goal of many experimental and computational efforts in Systems Biology. Separately the prediction of the structure of protein complexes by docking methods is a well-established scientific area. To date, docking programs have not been used to predict interaction partners. We provide a proof of principle for such an approach. Using a set of protein complexes representing known interactors in their unbound form, we show that a standard docking program can distinguish the true interactors from a background of 922 non-redundant potential interactors. We additionally show that true interactions can be distinguished from non-likely interacting proteins within the same structural family. Our approach may be put in the context of the proposed 'funnel-energy model'; the docking algorithm may not find the native complex, but it distinguishes binding partners because of the higher probability of favourable models compared with a collection of non-binders. The potential exists to develop this proof of principle into new approaches for predicting interaction partners and reconstructing biological networks.
authors.affiliation: Structural Biology and Biocomputing Programme, Spanish National Cancer Research Centre, Madrid, Spain.
authors.forename: Mark Nicholas
authors.initials: MN
authors.lastname: Wass
authors.forename: Gloria
authors.initials: G
authors.lastname: Fuentes
authors.forename: Carles
authors.initials: C
authors.lastname: Pons
authors.forename: Florencio
authors.initials: F
authors.lastname: Pazos
authors.forename: Alfonso
authors.initials: A
authors.lastname: Valencia
mesh_terms: D000465:Algorithms; D001665:Binding Sites; D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D030562:Databases, Protein; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D025941:Protein Interaction Mapping; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D011506:Proteins