Figure 1

Hierarchy of EGFR tail binding partners predicted by coarse-grained molecular modeling method. (A) Coarse-grained molecular modeling of EGFR C-terminal tail attached to the asymmetric model of EGFR kinase domain obtained from Zhang et al [45]. (B) Full-length coarse-grained molecular models of Shc (purple), Grb2 (yellow), PLCγ1 (green), and Stat5 (cyan). (C) Simplified systematic interaction profiling of the EGFR tyrosine family used in our study. In this model, EGFR has four cytoplasmic interaction partners, one binding site for each of Stat5 and Grb2, and two binding sites for each of Shc and PLCγ1. Coarse-grained docking method was used to develop the hierarchy of EGFR tail binding partners. Some possible docking methods between the four adaptors and EGFR include (D) PLCγ1 docked to pY992, (E) PLCγ1 docked to pY1173, (F) PLCγ1, Shc, and Grb2 simultaneously docked to EGFR at pY992, pY1148, and pY1068, respectively, and (G) Stat5, Shc, and Grb2 simultaneously docked to EGFR at pY992, pY1148, and pY1068, respectively.