title: Assessing the applicability of template-based protein docking in the twilight zone.
abstract: The structural modeling of protein interactions in the absence of close homologous templates is a challenging task. Recently, template-based docking methods have emerged to exploit local structural similarities to help ab-initio protocols provide reliable 3D models for protein interactions. In this work, we critically assess the performance of template-based docking in the twilight zone. Our results show that, while it is possible to find templates for nearly all known interactions, the quality of the obtained models is rather limited. We can increase the precision of the models at expenses of coverage, but it drastically reduces the potential applicability of the method, as illustrated by the whole-interactome modeling of nine organisms. Template-based docking is likely to play an important role in the structural characterization of the interaction space, but we still need to improve the repertoire of structural templates onto which we can reliably model protein complexes.
authors.affiliation: Joint IRB-BSC-CRG Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), c/ Baldiri Reixac 10-12, 08028 Barcelona, Spain.
authors.forename: Jacopo
authors.initials: J
authors.lastname: Negroni
authors.affiliation: Joint IRB-BSC-CRG Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), c/ Baldiri Reixac 10-12, 08028 Barcelona, Spain.
authors.forename: Roberto
authors.initials: R
authors.lastname: Mosca
authors.affiliation: Joint IRB-BSC-CRG Program in Computational Biology, Institute for Research in Biomedicine (IRB Barcelona), c/ Baldiri Reixac 10-12, 08028 Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Pg. Lluís Companys 23, 08010 Barcelona, Spain. Electronic address: patrick.aloy@irbbarcelona.org.
authors.forename: Patrick
authors.initials: P
authors.lastname: Aloy
mesh_terms: D030562:Databases, Protein; D062105:Molecular Docking Simulation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry; D012984:Software
chemical_list: D011506:Proteins