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Structure. 2016 Jan 5;24(1):116-126. doi: 10.1016/j.str.2015.10.025. Epub 2015 Dec 10.

Residues Coevolution Guides the Systematic Identification of Alternative Functional Conformations in Proteins.

Author information

1
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.
2
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; Instituci├│ Catalana de Recerca i Estudis Avan├žats (ICREA), Pg. Lluis Companys 23, 08011 Barcelona, Spain. Electronic address: patrick.aloy@irbbarcelona.org.
3
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.

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.

PMID:
26688214
DOI:
10.1016/j.str.2015.10.025
[Indexed for MEDLINE]
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