Research Article

Structure-Functional Prediction and Analysis of Cancer Mutation Effects in Protein Kinases

Figure 9

Computational modeling of the EGFR-L858R mutant. (a) The predicted structure of the L858R EGFR mutant. (b) A close-up of functionally important residues and interactions stabilizing the EGFR mutant. (c) A close-up comparison between conformations of the activation loop in the wild-type EGFR crystal structure (pdb entry 2J6M, green), L858R mutant crystal structure (pdb entry 2ITT, pink), and two best predicted mutant structures. The activation loop conformation of the two lowest energy predicted models of EGFR-L858R are shown in blue and cyan. The first predicted model of the complete EGFR-L858R protein structure has RMSD = 1.98 Å from the crystal structure (with the activation loop in blue). The second lowest energy model of the complete EGFR-L858R structure is within RMSD = 2.52 Å from the crystal structure (with the activation loop in cyan).
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