p38α mitogen-activated protein kinase (MAPK) undergoes autophosphorylation induced by the binding of TGFβ-activated kinase 1 binding protein 1 (TAB1) in myocardial ischemia. Investigation of the conformational transformations in p38α triggered by TAB1 binding is motivated by the need to find selective p38α activation inhibitors to treat myocardial ischemia. Herein, the conformational transformations of p38α were studied via all-atom accelerated molecular dynamics simulations and principal component analysis. With the binding of TAB1, the conformational changes of p38α auto-activation were characterized by the movement of the activation loop (A-loop) away from the αG helix toward the αF, αE helixes and L16-loop. In addition, a diverse intermediate state with an extensional and phosphorylated A-loop different from the transition intermediate state was explored. The conformational changes, including the A-loop alpha-structure breaking and the stronger hydrogen bond network formation, are accompanied by the extension of the A-loop and more intramolecular interactions in p38α. TAB1 correlates with other regions of p38α that are distal from the TAB1-binding site, including the A-loop, αC helix, and L16-loop, which regulates the intramolecular correlation of p38α. And, the phosphorylation further enhances the correlations between the A-loop and the other regions of p38α. The correlation results imply the regulation process of p38α conformational transformations. These findings will improve our understanding of the autophosphorylation of kinase and facilitate the development of selective inhibitors for the treatment of ischemic injury.