Abstract
The receiver domain of nitrogen regulatory protein C (NtrC) has two distinct conformations. The largest differences between the two conformations occur in the alpha4-helix. In addition to rigid body translocation and rotation, the alpha4-helix gains half a turn at one end and loses half a turn at the other end when the protein transforms from one conformation to another. The transition pathway between the two conformations is explored by the targeted molecular dynamics (TMD) algorithm in explicit solvent. It is segmented with four consecutive and distinct transition stages. Each transition stage has its own characteristic motion. We propose the reaction coordinates for each transition stage. By projecting the quasi-harmonic principal components along the first stage of the transition, we show that the dynamics of the nano-second time scale overlaps well with the beginning segment of the whole transition. The TMD pathway suggests that several transient hydrogen bonds help stabilize the intermediate structure and facilitate the transition.