I am studying protein-ligand interaction using Molecular Dynamics simulations. I have run MDs for the protein alone and the protein with different ligands. RMSD of the protein alone is around 0.39 nm. However, RMSDs of the bound protein between 0.3 to 0.37 nm. I have read in some comments that the RMSD value must be equal or less than 0.25 nm in order to be able to study protein-ligand interaction properly. Is that always true or there are exceptions? Is there any way to reduce the RMSD or that is impossible because of the nature of the protein? Finally, is it necessary to get very close ligand RMSD to protein RMSD in order to have a stable complex?