Although we did not attempt any hydrated docking , this method could easily be applied with hydrated ligands. This could have the additional benefit of accurately filling resolved water densities near the ligand density, preventing ligands from inaccurately being guided into this density. GOLEM and GlideEM currently feature explicit water placement during their respective pipelines, indicating that this may be an interesting avenue for further investigation in our own method. This may be especially helpful for systems like HSP90a, in which individual water molecules play essential and flexible roles in ligand binding . We also note that, in the current implementation in AutoDock-GPU, flexible side chains are treated as anchored ligands in the docking using the grid maps calculated for the ligand. This means that flexible side chains will also be guided by their associated density if it is left unmasked, potentially improving the modeling of ligand induced fit.