Abstract:MEK1 is an important signaling molecule in the Ras-Raf-MEK-ERK pathway. It plays an important role in tumorigenesis. Mutation of Raf and MEK1 genes of the pathway, resulting in the pathway being continuously activated is believed to be one of the important causes of unlimited tumor proliferation. Trametinib can effectively inhibit the activity of MEK1, and the loss of alpha helix in MEK1 structure will reduce the therapeutic effect of trametinib. In this experiment, the trajectories of action of E203K mutant and trametinib were analyzed by PCCA+ clustering analysis, Markov model and flux analysis, and it was found that E203K, P124S and wild type all undergo deconvolution into hydrogen bonding corner at the end of C166-S181 part near trametinib when interacting with trametinib, while there are differences in structural changes at the distal end.