Abstract
Non-receptor tyrosine kinase c-Src plays a critical role in numerous cellular signalling pathways. Activation of c-Src from its inactive to the active state involves large-scale conformational changes, and is controlled by the phosphorylation state of two major phosphorylation sites, Tyr416 and Tyr527. A detailed mechanism for the entire conformational transition of c-Src via phosphorylation control of Tyr416 and Tyr527 is still elusive. In this study, we investigated the inactive-to-active conformational change of c-Src by targeted molecular dynamics simulation. Based on the simulation, we proposed a dynamical scenario for the activation process of c-Src. A detailed study of the conformational transition pathway based on network analysis suggests that Lys321 plays a key role in the c-Src activation process.