Fig. 2. Free-energy surfaces for Cys797 alkylation by osimertinib in EGFR T790M (panel A) and in EGFR T790M/L718Q (panel B), calculated from umbrella sampling simulations at the SCC-DFTB/AMBER99SB level of QM/MM theory. The reaction coordinates (nucleophilic attack and proton transfer), are given in Å. Free energies are given in kcal mol–1, and the contour levels are set at 1 kcal mol–1 while dashed-contour lines are set every 4 kcal mol–1.
