Estimated values of free energy of binding are well correlated with inhibitory activities, including the parent binding was underestimated by approximately 0.8 kcal/mol. However, the docking procedure was performed in the EO 1428 absence of explicit water molecules, to avoid the almost insurmountable problem of simultaneous docking of three independent molecules, namely �C a given ligand and the two water molecules located in the binding pocket in the complex of CK2a with TBBt. But the absence of explicit water molecules, directly involved in ligand binding, Bretazenil causes systematic displacement of ligands toward Lys68 and Glu81. To further clarify this problem, an additional molecular dynamics was performed for each ligand in the presence of explicit water molecules. Analysis of the last 3 ns of each MD trace indicated that, for all ligands, their flexibility inside the CK2a binding pocket is comparable, and the root mean square fluctuation values, which are a measure of differences in ligand locations in snapshots of the MD trajectory, vary over a narrow. It follows that the binding pocket may readily adapt to the smaller ligands, and, consequently, the entropic contribution arising from ligand translational degrees of freedom is almost the same for all the ligands. For all nine brominated Bt derivatives the average location was found almost the same, and identical to that of TBBt in the crystal structure with CK2a. The only significant deviation was noted for the parent Bt, which was found inactive. The foregoing shows that all the halogenated Bt derivatives bind in the same orientation to CK2a. The correlation between experimental IC50 values and the energy terms, estimated both from the docking procedure, and directly from ab initio QM calculations for solvation, further demonstrate that the putative contribution of halogen bonding is significantly smaller than the other energy terms used in the calculations, if at all. In fact, detailed inspection of several conformational degrees of freedom for the protein showed that possible halogen bond-promoting conformations are not realized in the CK2a -TBBt complex, as illustrated by the His160 residue, for which a flip of the aromatic ring would have enabled interaction of Ne2 with a central halogen atom. The only halogen-bond promoting conformation was found for the p-Br interaction involving the Ne of Arg47 and a peripheral halogen atom of TBBt, as also found for one of the two protein molecules located in the crystal asymmetric unit. The propensity of the CK2a binding pocket to bind a halogenated ligand must be considered in terms of the topology of potential halogen-bond acceptors and the internal flexibility of the protein. We have performed a detailed analysis of all of 21 accessible structures of complexes of CK2 with ligands carrying at least one halogen atom. All of them were inspected using a 4 A �� threshold, to identify the distribution of distances between halogen atoms and proximal halogen bond acceptors. The resulting distribution of distances revealed the existence of a broad local maximum corresponding to a normal distribution with a mean value.