Figure 4.

Functional dynamics and protein mobility maps of the Tec subfamily of kinases. Functional dynamics and conformational mobility maps of the Tec kinase subfamily (Btk, Itk, and Bmx kinases) were computed by using PCA of MD simulations of the inactive crystal structures. Structural distribution of the protein kinase mobility is averaged over the two lowest frequency modes obtained from all-atom MD simulations. A surface-based protein representation is employed and colored (blue-to-red) according to the protein residue motilities (from more rigid-blue regions to more flexible-red regions). Two different close-up views of the regulatory hinge site formed by the αE-helix, αC-β4 loop, and the αC-helix are shown on (a), (b), (c), (d), (e), and (f). The autoinhibitory electrostatic interactions between a helical motif within the activation loop (Btk-R544 is shown in sticks) and the αC-helix (Btk-E445 is shown in sticks) are shown on (f). The conserved Btk-M450 and Itk-M410 located near the regulatory hinge site (shown in sticks on the right lower panel) are critical activating residues.