I tried modelling a new complex based on a template complex with the same DNA ligand but a few mutations in the protein. Initially I did the modelling the usual way and got good detectable RMSD (about 0.6) with the new mutated PDB (just the new protein, didn't have the DNA) and the original complex.
However when I tried to do the modelling considering DNA as a ligand (changed all DNA ATOMs to HETATM and modified alignment file with 9 appended '.'s - as my DNA is 9bp long), the new mutated complex, is nearly SAME as the template complex with minor changes in coordinates. (0.1 RMSD)
I don't understand that if I am using the same template and mutations, why is there so much of a difference (nearly 0.5 RMSD) between the two new complexes (with and without the DNA).
All RMSDs were done by superimposing structures in PyMOL.