Identification. In order to compare GIST results obtained from WaterKit ensembles and MD trajectories, we relied on the positions of high density water molecules, or called hydration sites, using the water oxygen density grid gO. The position of the first hydration site is identified by selecting the voxel with the highest water oxygen density. All the voxels within 2.5 Å of the first hydration site are then excluded from any future consideration. Then, the process is repeated for the next highest density voxel available, until no more voxels with density higher than 0.1 density / bulk density are available.