Effect of double mutations T790M/L858R on conformation and drug-resistant mechanism of epidermal growth factor receptor explored by molecular dynamics simulations.

ABSTRACT: Epidermal growth factor receptor (EGFR) is one of the most promising targets for the treatment of cancers. Double mutations T790M/L858R lead to different degrees of drug resistance toward inhibitors. In this study, molecular dynamics (MD) simulations followed by principal component analysis are performed to study the conformational changes of EGFR induced by T790M/L858R. The results suggest that T790M/L858R cause obvious disturbance of the structural stability of EGFR. Molecular mechanics-Poisson Boltzmann surface area (MM-PBSA) and residue-based free energy decomposition methods are integrated to explore the drug-resistant mechanism of T790M/L858R toward inhibitors. The results show that the decrease in van der Waals interactions of inhibitors with the mutated EFGR relative to the wild-ty

SUBMITTER: Yan F 

PROVIDER: S-EPMC9091310 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature