An energy landscape approach predicts the conformational changes of the configurations of the regulatory domain of the protein nuclear factor of activated T cells (NFAT) caused by phosphorylation of specific multiple sites. Structurally local effects and secondary structural changes are modeled using all-atom Brownian dynamics to investigate the changes of the backbone torsional distributions upon phosphorylation. For tertiary and global changes, we employ a coarse-grained model to sample ensembles of conformations both with and without phosphorylation. At the secondary structure level, phosphorylation moderately increases the helical propensity and gives a more rigid local backbone conformation. The tertiary effects of phosphorylation caused by the extensive charge modification are more pronounced and collectively change the conformation of the regulatory domain of NFAT from a flexible globular ensemble to a rather rigid helical bundle, blocking access to the nuclear localization sequence. These studies give computational support to one scenario conjectured from experiments.