Overall, our results highlight the high-energy characteristics of this Thr58 associated conserved water when co-existing with a SII-P binder. Therefore, there resides a great potential in targeting this water molecule. However, this is not a trivial task as the pocket is highly dynamic , and it will require an optimally designed compound that is capable to replace the water without simultaneously compromising the binding affinity of the small molecule in other regions. To achieve this goal, tremendous efforts from the medicinal chemists and other scientists are required. Finally, we would like to emphasize that one should not have any unrealistic expectations related to the conserved water, it will not solely define the binding affinity of a compound, it is only one piece of a much larger puzzle.