Structure-Functional Prediction and Analysis of Cancer Mutation Effects in Protein Kinases
Figure 12
Functional dynamics and structural map of inactivating cancer mutants in different kinase genes. Functional dynamics and conformational mobility maps of the kinase mutants were computed using MD simulations of the crystal structures. (a) The dynamic profile of the MAP2K4 kinase (pdb id 3alo) with the mapped activating mutations (Q142L, R134Q) and inactivating mutations (P326L, S251N, and N234I). (b) The dynamics profile of EPHA3 (pdb id 2qoq) with the mapped inactivating mutations (R728L, K761N, D6778E, G766E, and D806N). (c) The dynamics profile of the DAPK3 kinase (pdb id 3bhy) with the mapped inactivating mutations T112M, D161N, and P216S. (d) The dynamics profile of the TRKB kinase (pdb id 4asz) with the mapped inactivating mutations T695I and D751N. A surface-based protein representation is employed, colored (blue-to-red) according to the protein residue motilities (from more rigid-blue regions to more flexible-red regions).
