Despite the fact that polarizability of water is different in the bulk and in protein, simulations of protein-ligand complexes are mostly carried out in nonpolarizable water media. We present oxime (HI-6) unbinding from the active site gorge of AChE, known to be strongly influenced by intermolecular cation-pi, hydrogen bridge (HB) and water bridge (WB) interactions and by molecular simulations with effective polarization in polarizable mean-field model of TIP3P water. Enabled by the recent availability of a method of obtaining microkinetics of rare events, we set out to investigate the rate constants of unbinding transitions from one basin to the other through a combination of metadynamics and hyperdynainics simulations. The results underpin the importance of electronic polarization effects on the pathways, potential of mean force, rate constants, and HB and WB dynamics of unbinding transitions of a drug molecule ligated to protein interior. The method is also applicable to unravel the binding mechanisms.