The new inhibition strategy of the p۳۸ MAP Kinase protein by using mutagenesis and COXH۱۱ inhibitor

Mitogen-activated kinase proteins family is involved in a variety of cellular functions, such as apoptosis,differentiation, transcription, and proliferation. Besides, p۳۸ MAP kinases are associated with regulatingcellular responses to various stimulus activities, like pro-inflammatory cytokines, heat shock, mitogens, andosmotic stress. In this study, we mutated the three amino acids of the p۳۸ protein active site. Then inhibitorof COXH۱۱ was docked to the binding pocket of p۳۸ protein and subsequently, molecular dynamics (MD)simulations were carried out. The COXH۱۱ inhibitor is a pyrazolo benzothiazine-based compound that hasfour rings and has an inhibitory effect on the P۳۸ MAP kinase protein. Gromacs software version ۵.۰.۱ wasused to investigate mutation effects. The MD simulation time was set at ۲۵۰ nanoseconds and the p۳۸ proteinmolecule dissolved in the water of the TIP۳P model. The results showed mutation caused p۳۸ protein to formmore non-bonded interactions with COXH۱۱ inhibitor. The significant effects of COXH۱۱ inhibitor on thep۳۸ protein can be the potential novel strategy for the treatment of related diseases

کلیدواژه ها:

P۳۸ MAP kinases ، Molecular Dynamic Simulation ، Protein Mutation