a, Phylogenetic tree of murine CMGC group kinases. The CDK family is boxed in orange, and the p38 family in green. b, c, Plot of the distance (in Å) between RO3306 and the ATP-binding site along the 10 aMD simulations of CDK1 and p38γ (b), and p38α and CDK2 (c), together with representative RO3306-bound conformations. Spontaneous binding of RO3306 occurs in 5/10 simulations with p38γ, 2/10 with CDK1, 0/10 with p38α, and 1/10 with CDK2. d, Comparison of spontaneous RO3306-binding events observed in 500 ns of aMD simulation time for p38γ and p38δ. e, Representative binding pathway obtained from aMD simulations of RO3306 with p38γ (top) and CDK1 (bottom). f, p38γ phosphorylation sites detected in Rb by an in vitro kinase assay followed by mass spectrometry.