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Fig. 1 | BMC Cancer

Fig. 1

From: Compounds identified by virtual docking to a tetrameric EGFR extracellular domain can modulate Grb2 internalization

Fig. 1

Virtual screening methods identify candidate EGFR multimer stabilizers. Panel a depicts a simple cartoon showing unliganded EGFR monomer in the context of the plasma membrane (PM), the EGF-bound EGFR upright dimer, and the EGF-bound prone tetramer. Panel b depicts a structural model of two canonical back-to-back EGF-bound EGFR dimers (extracellular portion, each with one monomer in ribbons and the other in spacefill) that further multimerize to form a tetramer along a novel head-to-head interface (dashed line). Each monomer is colored by domain: I–cyan, II–orange, III–green, IV–pink, bound EGF–purple, with the chains of one canonical dimer in dark shades and the other in light shades. Dashed ovals indicated the approximate positions of the three docking boxes (2, 3 and 1) that were explored to identify small molecule ligands proposed to bind to and stabilize the novel interface. c A detailed view of Box 2 illustrates the boundaries in which docked molecules must be contained (purple) and in which the center of the docked molecules must be located (green). Identified hits that docked in Box 2 are shown in ball-and-stick representation with the carbons colored in yellow (F5230-0424) or cyan (F2738-2186) or white (F2573-0380) and other atoms in CPK. Boxes 3 and 1 are similarly detailed in panels d and e; hits are shown with the carbons in white or yellow (Box 3: F0922-0900 and F3385-3143 respectively, Box 1: F3109-0096). The views in panels c-e have slightly different rotations to optimally show the orientation of the boxes and ligands. Molecular details and interactions for each of the ligands are shown in Fig. 5

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