Molecular dynamics use in personalized cancer medicine: Example of MET Y501C mutation

We explored a possible new method for prediction of activating mutations in cancer-related proteins. This method is based on elucidation of flexibility of proteins associated in activating complexes. Based on the theory of intermediate binding complexes, the binding process is not only related to the three-dimensional structure of proteins, but also to the four-dimensional set of possible conformations allowed by the flexible regions of the involved members of the associated complex. Using molecular dynamics simulations, we found that an Y501C mutation in the MET gene might activate it. Using this information, a specific drug that functioned as a potent MET inhibitor was prescribed and had a salutary impact on the tumor.