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Receptor tyrokine kinases are critical regulators of signal transduction pathways mediating cellular homeostasis. Enhanced kinase activities via mutation and other genetic alternations have been observed in many human cancers. We performed a 4 ns molecular dynamics (MD) simulation of the kinase domain of fibroblast growth factor receptor 1 (FGFRl) to study the mechanism that controls its activation. Our simulation revealed the key atomic events that allow substrate access and kinase activation. This dynamic information will facilitate the design of new inhibitors for use in the treatment of cancer.