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Updated: Mar 28, 2026

Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues
Published on: July 14, 2015
Residues Coevolution Guides the Systematic Identification of Alternative Functional Conformations in Proteins
Pedro Sfriso1, Miquel Duran-Frigola1, Roberto Mosca1
1Institute 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.
None:
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.
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