title: Validated Conformational Ensembles Are Key for the Successful Prediction of Protein Complexes.
abstract: Conformational fluctuations in proteins play key roles in their functions and interactions. In this work, validated conformational ensembles for ubiquitin have been used in docking trials. The ensembles were used in a systematic predictive study of known ubiquitin complexes by applying a cross-docking strategy against the bound structure of each partner. The global docking predictions obtained with the complete ubiquitin ensembles were significantly better than those obtained with the crystallographic structure of free ubiquitin. Importantly, in all cases we identified an individual ensemble member that performed equally well, or even better, than the bound structure of ubiquitin. These results unequivocally demonstrate that, for proteins that recognize binding partners by conformational selection, the availability of conformational ensembles can greatly improve the performance of automatic docking predictions. Our results highlight the need for docking methodologies to capitalize on validated ensemble representations of biomacromolecules.
authors.affiliation: Joint BSC-IRB research programme in Computational Biology, Barcelona Supercomputing Center (BSC) , Jordi Girona 29, Barcelona 08034, Spain.|Computational Bioinformatics, National Institute of Bioinformatics (INB) , Jordi Girona 29, Barcelona 08034, Spain.
authors.forename: Carles
authors.initials: C
authors.lastname: Pons
authors.affiliation: Joint BSC-IRB Research Programme in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona) , Baldiri Reixac 10, 08028 Barcelona, Spain.
authors.forename: R Bryn
authors.initials: RB
authors.lastname: Fenwick
authors.affiliation: Joint BSC-IRB research programme in Computational Biology, Barcelona Supercomputing Center (BSC) , Jordi Girona 29, Barcelona 08034, Spain.|Joint BSC-IRB Research Programme in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona) , Baldiri Reixac 10, 08028 Barcelona, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Esteban-Martín
authors.affiliation: Joint BSC-IRB Research Programme in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona) , Baldiri Reixac 10, 08028 Barcelona, Spain.|Institució Catalana de Recerca i Estudis Avançats (ICREA) , Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Salvatella
authors.affiliation: Joint BSC-IRB research programme in Computational Biology, Barcelona Supercomputing Center (BSC) , Jordi Girona 29, Barcelona 08034, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Fernandez-Recio