Fig. 3

Structural analysis of EGFR^19del+G724S. a Binding site of rociletinib bound EGFR (PDB ID: 5UWD). b Alignment of the rociletinib bound EGFR-binding site (blue, PDB ID: 5UWD) with exon 20-mutant EGFR (white, PDB ID: 4LRM) that reveals steric hindrance of third-generation TKIs with the glycine-rich loop and the adjacent sheet β1 upon a perturbed network between helix αC, ELREA motif, and glycine-rich loop. c Comparison of MD simulations of osimertinib bound EGFR^WT (left), EGFR^G724S (right) (based on PDB ID: 4ZAU). d Comparison of MD simulations of osimertinib bound EGFR^19del (left) or EGFR^19del+G724S (right) (based on PDB ID: 4ZAU)