Structural Analysis of Interactions between Epidermal Growth Factor Receptor (EGFR) Mutants and Their Inhibitors

People’s lives and health are gravely threatened by non-small-cell lung cancer (NSCLC). Mutations in epidermal growth factor receptor (EGFR), a transmembrane tyrosine kinase, considered one of the causes NSCLC. Tyrosine kinase inhibitors (TKIs) typically used to treat patients with EGFR mutations. In this study, Gefitinib, member first generation TKIs, was an single-point mutation (single mutant, SM). Patients harboring additional T790M mutations domain were resistant Gefitinib. Then, L858R/T790M double (double DM) treated second such as Afatinib. Here, we constructed four computational models uncover structural basis between mutants (SM corresponding (Gefitinib Afatinib). The binding energy G-SM (representing Gefitinib complex SM) system larger than that G-DM (Representing system. Gefitinib’s affinity L792 M793 drastically reduced longer side chain M790 system, which pushed outside pocket. Additionally, A-DM system’s higher system’s. Afatinib, unlike induced P-loop region move downwards decrease pocket entrance size accommodate Afatinib properly stably (Afatinib These results details interactions its shed light on design new inhibitors.