Mechanism of Drug Efficacy Within the EGF Receptor Revealed by Microsecond Molecular Dynamics Simulation

作者：Wan Shunzhou; Wright David W; Coveney Peter V^*

来源：Molecular Cancer Therapeutics, 2012, 11(11): 2394-2400.

DOI：10.1158/1535-7163.MCT-12-0644-T

The EGF receptor (EGFR) regulates important cellular processes including proliferation, differentiation, and apoptosis. EGFR is frequently overexpressed in a range of cancers and is associated with disease progression and treatment. Clinical studies have shown that EGFR mutations confer tumor sensitivity to tyrosine kinase inhibitors in patients with non-small cell lung cancer. In this study, we have conducted molecular dynamics simulations over several microseconds for wild-type and L858R mutant forms of EGFR in the ligand-free state. Close inspection of the conformations and interactions within the binding pocket reveals, converse to the wild type, that the mutant EGFR prefers to bind gefitinib, a targeted anticancer drug, rather than ATP, offering an explanation for why gefitinib is more effective in patients with EGFR mutations than those without. Mol Cancer Ther; 11(11); 2394-400.

• 出版日期2012-11