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dc.contributor.authorPallara, Chiara
dc.contributor.authorRueda, Manuel
dc.contributor.authorAbagyan, Ruben
dc.contributor.authorFernández-Recio, Juan
dc.contributor.otherBarcelona Supercomputing Center
dc.identifier.citationPallara, Chiara [et al.]. Conformational Heterogeneity of Unbound Proteins Enhances Recognition in Protein–Protein Encounters. "Journal of Chemical Theory and Computation", 20 Juny 2016, vol. 12, núm. 7, p. 3236-3249.
dc.description.abstractTo understand cellular processes at the molecular level we need to improve our knowledge of protein−protein interactions, from a structural, mechanistic, and energetic point of view. Current theoretical studies and computational docking simulations show that protein dynamics plays a key role in protein association and support the need for including protein flexibility in modeling protein interactions. Assuming the conformational selection binding mechanism, in which the unbound state can sample bound conformers, one possible strategy to include flexibility in docking predictions would be the use of conformational ensembles originated from unbound protein structures. Here we present an exhaustive computational study about the use of precomputed unbound ensembles in the context of protein docking, performed on a set of 124 cases of the Protein−Protein Docking Benchmark 3.0. Conformational ensembles were generated by conformational optimization and refinement with MODELLER and by short molecular dynamics trajectories with AMBER. We identified those conformers providing optimal binding and investigated the role of protein conformational heterogeneity in protein−protein recognition. Our results show that a restricted conformational refinement can generate conformers with better binding properties and improve docking encounters in medium-flexible cases. For more flexible cases, a more extended conformational sampling based on Normal Mode Analysis was proven helpful. We found that successful conformers provide better energetic complementarity to the docking partners, which is compatible with recent views of binding association. In addition to the mechanistic considerations, these findings could be exploited for practical docking predictions of improved efficiency.
dc.format.extent14 p.
dc.publisherAmerican Chemical Society
dc.subjectÀrees temàtiques de la UPC::Enginyeria biomèdica
dc.subject.lcshProtein engineering
dc.subject.lcshMolecular dynamics
dc.subject.lcshCellular series
dc.subject.otherGeneration of Protein Conformational Ensembles.
dc.subject.otherCellular processes
dc.subject.otherFast Fourier Transform (FFT) algorithms
dc.titleConformational Heterogeneity of Unbound Proteins Enhances Recognition in Protein–Protein Encounters
dc.subject.lemacEnginyeria de proteïnes
dc.subject.lemacDinàmica molecular
dc.description.peerreviewedPeer Reviewed
dc.rights.accessOpen Access
dc.description.versionPostprint (author's final draft)
upcommons.citation.publicationNameJournal of Chemical Theory and Computation

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