Background and purpose of the study: p38α is a member of mitogen-activated protein kinases (MAPK) considered as a prominent target in development of anti-inflammatory agents. Any abnormality in the phosphorylation process leads to the different human diseases such as cancer, diabetes and inflammatory diseases. Several small molecule p38α inhibitors have been developed up to now. In this regard, structural elucidation of p38 inhibitors needs to be done enabling us in rational lead development strategies.
Methods: Various interactions of three potent inhibitors with p38α active site have been evaluated in terms of binding energies and bond lengths via density function theory and MD simulations.
Results: Our comparative study showed that both ab initio and MD simulation led to the relatively similar results in pharmacophore discrimination of p38α inhibitors.
Conclusion: The results of the present study may find their usefulness in pharmacophore based modification of p38α inhibitors.