We develop an approach by which reliable estimates of the transfer entropy can be obtained from the variance-covariance matrix of atomic fluctuations, which converges quickly and retains sensitivity to the full chemical profile of the biomolecular system. We validate our method on ERK2, a well-studied kinase involved in the MAPK signaling cascade for which considerable computational, experimental, and mutation data are available. We present the results of transfer entropy analysis on data obtained from molecular dynamics simulations of wild-type active and inactive ERK2, along with mutants Q103A, I84A, L73P, and G83A. We show that our method is systematically consistent within the context of other approaches for calculating transfer entropy, and we provide a method for interpreting networks of interconnected residues in the protein from a perspective of allosteric coupling. We introduce new insights about possible allosteric activity of the extreme N-terminal region of the kinase, and we describe evidence that suggests that activation may occur by different paths or routes in different mutants. Our results highlight systematic advantages and disadvantages of each method for calculating transfer entropy and show the important role of transfer entropy analysis for understanding allosteric behavior in biomolecular systems.