Dan K. Vanatta, Diwakar Shukla, Morgan Lawrenz & Vijay S. Pande
Nature Communications, 6, Article number: 7283, 2015. doi:10.1038/ncomms8283
Publication year: 2015

Bacterial Signaling, Nature Communications, 2015


Recent successes in simulating protein structure and folding dynamics have demonstrated the power of molecular dynamics to predict the long timescale behavior 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 give a new dynamic picture of the activation for the key bacterial signaling 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.