Should I add hydrogens to the input ligand?
No need to add hydrogens to the ligand either – eHiTS will do that. But if the input DOES have already H atoms, then eHiTS will use the given POSITIONS, but it may switch the protonation states treating some of those as a lone pair rather than hydrogen. This feature (“use H when given, generate when not given”) allows the user more control. If the user has generated the H positions from reliable source (e.g. QM modelling, minimization), then it is better to use those. However, it is not worth using OpenBabel, Corina or other simple modelling tool to generate them, because eHiTS’ internal knowledge base will do as good or better job and will definitely match better its own training that way.