title: Residues Coevolution Guides the Systematic Identification of Alternative Functional Conformations in Proteins.
abstract: We present here a new approach for the systematic identification of functionally relevant conformations in proteins. Our fully automated pipeline, based on discrete molecular dynamics enriched with coevolutionary information, is able to capture alternative conformational states in 76% of the proteins studied, providing key atomic details for understanding their function and mechanism of action. We also demonstrate that, given its sampling speed, our method is well suited to explore structural transitions in a high-throughput manner, and can be used to determine functional conformational transitions at the entire proteome level.
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), C/Baldiri Reixac 10, 08028 Barcelona, Spain; Joint BSC-IRB Research Program in Computational Biology, C/Baldiri Reixac 10, 08028 Barcelona, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Sfriso
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), C/Baldiri Reixac 10, 08028 Barcelona, Spain; Joint BSC-IRB Research Program in Computational Biology, C/Baldiri Reixac 10, 08028 Barcelona, Spain.
authors.forename: Miquel
authors.initials: M
authors.lastname: Duran-Frigola
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), C/Baldiri Reixac 10, 08028 Barcelona, Spain; Joint BSC-IRB Research Program in Computational Biology, C/Baldiri Reixac 10, 08028 Barcelona, Spain.
authors.forename: Roberto
authors.initials: R
authors.lastname: Mosca
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), C/Baldiri Reixac 10, 08028 Barcelona, Spain; Joint BSC-IRB Research Program in Computational Biology, C/Baldiri Reixac 10, 08028 Barcelona, Spain.
authors.forename: Agustí
authors.initials: A
authors.lastname: Emperador
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), C/Baldiri Reixac 10, 08028 Barcelona, Spain; Joint BSC-IRB Research Program in Computational Biology, C/Baldiri Reixac 10, 08028 Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Pg. Lluis Companys 23, 08011 Barcelona, Spain. Electronic address: patrick.aloy@irbbarcelona.org.
authors.forename: Patrick
authors.initials: P
authors.lastname: Aloy
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), C/Baldiri Reixac 10, 08028 Barcelona, Spain; Joint BSC-IRB Research Program in Computational Biology, C/Baldiri Reixac 10, 08028 Barcelona, Spain; Department of Biochemistry and Molecular Biology, University of Barcelona, Av. Diagonal 647, 08028 Barcelona, Spain. Electronic address: modesto.orozco@irbbarcelona.org.
authors.forename: Modesto
authors.initials: M
authors.lastname: Orozco
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D019143:Evolution, Molecular; D006801:Humans; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D011487:Protein Conformation