title: A network of molecular switches controls the activation of the two-component response regulator NtrC.
abstract: 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.
authors.affiliation: Department of Chemistry, Stanford University, Stanford, California 94305, USA.
authors.forename: Dan K
authors.initials: DK
authors.lastname: Vanatta
authors.affiliation: 1] Department of Chemistry, Stanford University, Stanford, California 94305, USA [2] SIMBIOS NIH Center for Biomedical Computation, Stanford University, Stanford, California 94305,USA [3] Department of Chemical and Bimolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, Illionios 61801, USA.
authors.forename: Diwakar
authors.initials: D
authors.lastname: Shukla
authors.affiliation: Department of Chemistry, Stanford University, Stanford, California 94305, USA.
authors.forename: Morgan
authors.initials: M
authors.lastname: Lawrenz
authors.affiliation: 1] Department of Chemistry, Stanford University, Stanford, California 94305, USA [2] SIMBIOS NIH Center for Biomedical Computation, Stanford University, Stanford, California 94305,USA.
authors.forename: Vijay S
authors.initials: VS
authors.lastname: Pande
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D008390:Markov Chains; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D051922:PII Nitrogen Regulatory Proteins / Q000737:chemistry* / Q000378:metabolism; D060066:Protein Interaction Maps; D017434:Protein Structure, Tertiary
chemical_list: D001426:Bacterial Proteins; D051922:PII Nitrogen Regulatory Proteins