Conformational Transition Pathways of Epidermal Growth Factor Receptor Kinase Domain from Multiple Molecular Dynamics Simulations and Bayesian Clustering.

ABSTRACT: The epidermal growth factor receptor (EGFR) is aberrantly activated in various cancer cells and an important target for cancer treatment. Deep understanding of EGFR conformational changes between the active and inactive states is of pharmaceutical interest. Here we present a strategy combining multiply targeted molecular dynamics simulations, unbiased molecular dynamics simulations, and Bayesian clustering to investigate transition pathways during the activation/inactivation process of EGFR kinase domain. Two distinct pathways between the active and inactive forms are designed, explored, and compared. Based on Bayesian clustering and rough two-dimensional free energy surfaces, the energy-favorable pathway is recognized, though DFG-flip happens in both pathways. In addition, another pathway

SUBMITTER: Li Y 

PROVIDER: S-EPMC4132868 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature