In the bacterium Bacillus subtilis, manganese homeostasis is regulated by the transcription factor MntR. The DNA-binding affinity of this transcriptional regulator is allosterically modified by manganese binding.[1] Although ample experimental data about this protein is available, including a large number of X-ray structures, [2, 3] the specific mechanism by which manganese binding allosterically modifies the affinity of MntR for DNA is still a puzzle. In order to shed light on the mentioned mechanism, we will couple the results of our computational simulations with several experimental methods, including NMR. The dynamical and structural properties of MntR in its apo form, as well as in complexes with Mn2+ ions, were studied by molecular dynamics simulations. The interaction of protein and manganese ions was parametrized using a bonded model, for which parameters were developed using quantum mechanics calculations. In addition to MD simulations of apo MntR and metal-MntR complexes, MntR-DNA complexes (for which crystal structures aren’t available) were also prepared and simulated. In order to extract as much useful information as possible from MD simulations, diverse statistical analyses were applied with the goal to identify key differences in protein dynamics between the manganese-free and manganese-bound structures of the protein.
