Fig. 1From: Compounds identified by virtual docking to a tetrameric EGFR extracellular domain can modulate Grb2 internalizationVirtual 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. 5Back to article page