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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms*
  • Amino Acid Sequence
  • Animals
  • Evolution, Molecular*
  • Humans
  • Molecular Dynamics Simulation*
  • Molecular Sequence Data
  • Protein Conformation