F. Musiani, B. Bertosa, A. Magistrato, B. Zambelli, P. Turano, V. Losasso, C. Micheletti, S. Ciurli and P. Carloni
Computational Study of the DNA-Binding Protein Helicobacter pylori NikR: The Role of Ni2+
J. Chem. Theory Comput., 2010 6 3503-3515
Link to online article

ABSTRACT
An integrated approach, combining atomistic molecular dynamics simulations, coarsegrained models, and solution NMR, was used to characterize the internal dynamics of HpNikR, a Ni-dependent transcription factor. Specifically, these methods were used to ascertain how the presence of bound Ni2+ ions affects the stability of the known open, cis, and trans forms observed in the crystal structures of this protein as well as their interconversion capability. The consensus picture emerging from all the collected data hint at the interconversion of NikR among the three types of conformations, regardless of content of bound Ni2+. On the basis of atomistic and coarse-grained simulations, we suggest that the interconversion capability is particularly effective between the cis and the open forms and appreciably less so between the trans conformer and the other two forms. The presence of the bound Ni2+ ions does, however, affect significantly the degree of the correlations on the two DNA-binding domains of NikR, which is significantly suppressed as compared to the apo form. Overall, the findings suggest that the binding of HpNikR to DNA occurs through a sophisticated multistep process that might involve both a conformational selection and an induced fit.