Could you provide superimposition picture or any other details that might be helpful? For instance,iIs your ligand highly flexible? How are you calculating RMSD value?

Hi Honey Dzikri Marhaeny;

Have you tried to change the size of the grid box? Otherwise you can use Pymol: open the two files (the autodock output file .pdbqt and the XR ligand file), then type: align file name1, file name2. (in the command input area) If your RMSD is still high, you may change the target's pdb file outright.

Hi

Before I faced the same problem, Can you tell me how many rotatable bonds in your small molecule to be able to guide you in suitable way?