I have few problems related with ligand preparation protocol...Firstly if i prepared ligands by using small molecule tool "prepare Ligand" (default) which gave 5663 poses out of 19 input ligands.and then i did docking using LibDock(default 255conformers) with "no minimization" .i got results for nearly all the poses.

However, if i open ligand file individually, minimize them and use those minimized ligands for "prepare ligands" in small molecule task, i get only 60 poses for the same set of ligands(input 19ligands). Results of Docking are also different from the previous case...

Now i really donot understand what i should do?? what is the protocol for preparation of ligands prior to libdock considering that i dont want to minimize ligands within the active site..Do i need to minimize ligands before preparing them, coz if i do after preparing them the number of ligands is too much. and i dont want to  minimize ligands with in the binding cavity as again the number of ligands 5663 would be very time consuming.

Moreover, redocking of minimized ligand then prepare ligand and then docking yielded good RMSD for a particular target where as in another target it yielded good RMSD as with the first case. .