TY - JOUR
T1 - Validated conformational ensembles are key for the successful prediction of protein complexes
AU - Pons, Carles
AU - Fenwick, R. Bryn
AU - Esteban-Martín, Santiago
AU - Salvatella, Xavier
AU - Fernandez-Recio, Juan
PY - 2013/3/12
Y1 - 2013/3/12
N2 - 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.
AB - 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.
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U2 - 10.1021/ct300990h
DO - 10.1021/ct300990h
M3 - Article
AN - SCOPUS:84874870176
SN - 1549-9618
VL - 9
SP - 1830
EP - 1837
JO - Journal of Chemical Theory and Computation
JF - Journal of Chemical Theory and Computation
IS - 3
ER -