We studied the complexes of cAMP-dependent protein kinase with three transition state analogues, namely MgF3, AlF4 and AlF3. These analogues are meaningfully different among themselves and from the native transition state (PO3), allowing for the discrimination, in terms of charge and geometry, of what contributes more to the binding energy. We show that PKA prefers to bind AlF4 (same charge, different geometry) over AlF3 (different charge, same geometry), in accordance with experimental data and the charge balance concept. We also detected a correlation between the binding energy and the amount of charge transferred from the TSAs to the enzyme. (C) 2013 Elsevier B.V. All rights reserved.