Structure-Functional Prediction and Analysis of Cancer Mutation Effects in Protein Kinases
Figure 2
Functional dynamics and protein mobility maps of the EGFR subfamily of kinases. Conformational mobility maps of the Egfr/ErbB tyrosine kinase subfamily (EGFR/Her1, ErbB2/Her2, ErbB3/Her3, and ErbB4/Her4 kinases) were computed using MD simulations of the inactive crystal structures. Structural distribution of the protein kinase mobility is averaged over the two lowest frequency modes. 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). A close-up of the regulatory hinge site formed by the αE-helix, αC-β4 loop, and the αC-helix is shown on the right panel. Structurally rigid αE-helix and αC-β4 loop are linked at the hinge site to a more flexible αC-helix. The autoinhibitory intramolecular clamp formed between the αC-helix and a short α-helix of the activation loop is a conserved feature of the EGFR kinases.