title: Segmented transition pathway of the signaling protein nitrogen regulatory protein C.
abstract: Recent advances in experimental methods provide increasing evidence that proteins sample the conformational substates that are important for function in the absence of their ligands. An example is the receiver domain of nitrogen regulatory protein C, a member of the phosphorylation-mediated signaling family of "two-component systems." The receiver domain of nitrogen regulatory protein C samples both inactive conformation and the active conformation before phosphorylation. Here we determine a possible pathway of interconversion between the active state and the inactive state by targeted molecular dynamics simulations and quasi-harmonic analysis; these methods are used because the experimental conversion rate is in the high microsecond range, longer than those that are easily accessible to atomistic molecular dynamics simulations. The calculated pathway is found to be composed of four consecutive stages described by different progress variables. The lowest quasi-harmonic principal components from unbiased molecular dynamics simulations on the active state correspond to the first stage, but not to the subsequent stages of the transition. The targeted molecular dynamics pathway suggests that several transient nonnative hydrogen bonds may facilitate the transition.
authors: Department of Biochemistry, Brandeis University, Howard Hughes Medical Institute, Waltham, MA 02454, USA.
authors: Ming
authors: M
authors: Lei
authors: Janice
authors: J
authors: Velos
authors: Alexandra
authors: A
authors: Gardino
authors: Alexsandr
authors: A
authors: Kivenson
authors: Martin
authors: M
authors: Karplus
authors: Dorothee
authors: D
authors: Kern
mesh_terms: D003198:Computer Simulation; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D051922:PII Nitrogen Regulatory Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011487:Protein Conformation; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D029968:Escherichia coli Proteins; D051922:PII Nitrogen Regulatory Proteins; D014157:Transcription Factors; C497876:glnG protein, E coli