EGFR and lung carcinoma: L718Q mutant EGFR escapes covalent inhibition by stabilizing a non-reactive conformation of the lung cancer drug osimertinib†
†Electronic supplementary information (ESI) available: pKa shift for Cys797; geometries of TSs identified with QM/MM calculations; analysis of the minimum free-energy path for Cys797 alkylation; analysis of MD replicas; convergence for US simulations; replica of simulation of Cys797 alkylation; conformational FESs obtained from each MD replica. See DOI: 10.1039/c7sc04761d