The analysis of hydration sites shows that water molecule positions predicted with both methods tend to closely match structural structural features of the bound ligand PU2 (Fig. 6). Hydration sites W5-W7 overlap with the positions of the atoms in the purine ring (Fig. ). The strongest is W5, which is stabilized by a HB interaction with Asp93 and displaced by the ligand amine group. The weakest is W7, which is displaced by the fluorine atom of PU2. WaterKit predicts a stable W6 positioned very closely (0.9 Å) to where N1 nitrogen of the ligand purine is found and displaces it upon binding (Fig. ). This prediction is unmatched by MD average results (Fig. ) because of the instability of individual MD replicates, which show a high degree of variability in oxygen density (gO: 0.1 -39.3) and distances from the N1 nitrogen position between 0.6 and 1.6 Å. Finally, both MD and WaterKit predict a structured network of weakly bound water molecules in the hydrophobic pocket engaged by the dimethoxybenzene moiety of the ligand (Fig. ). An interesting finding of the hsp90α analysis is that despite the presence of numerous disordered hydroxyls in the binding site (Ser37, Tyr124, Thr169, Thr137), keeping hydrogen positions fixed during the WaterKit simulation (i.e.: when calculating grid maps) does not affect its accuracy. The use of the non-directional HB donor/acceptor probe Vina O_DA is able to compensate for this limitation (Fig. ), so predictions can match fairly closely those obtained with MD simulations, reproducing almost entirely the water network with great accuracy.