A network of molecular switches controls the activation of the two-component response regulator NtrC

Nat Commun. 2015 Jun 15;6:7283. doi: 10.1038/ncomms8283.


Recent successes in simulating protein structure and folding dynamics have demonstrated the power of molecular dynamics to predict the long timescale behaviour of proteins. Here, we extend and improve these methods to predict molecular switches that characterize conformational change pathways between the active and inactive state of nitrogen regulatory protein C (NtrC). By employing unbiased Markov state model-based molecular dynamics simulations, we construct a dynamic picture of the activation pathways of this key bacterial signalling protein that is consistent with experimental observations and predicts new mutants that could be used for validation of the mechanism. Moreover, these results suggest a novel mechanistic paradigm for conformational switching.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / metabolism
  • Markov Chains
  • Models, Molecular
  • Molecular Dynamics Simulation*
  • PII Nitrogen Regulatory Proteins / chemistry*
  • PII Nitrogen Regulatory Proteins / metabolism
  • Protein Interaction Maps*
  • Protein Structure, Tertiary


  • Bacterial Proteins
  • PII Nitrogen Regulatory Proteins