Dear Govinda Rao Dabburu ,

It really depends on the context of your complex. RMSD is a simple measure, in which we evaluate how much a structure variated when compared to its initial state. Thus, if not analyzed in context, we can not safely assume anything. Some lines of thinking, nevertheless, explain the following:

- Generally, stable protein-ligand complexes have lower RMSD. Generally.

- Generally, low RMSD is often associated with a low-energy state, which would be close to a WT conformation. In a protein-ligand complex, the logic would be similar, where it would be the most frequent conformation assumed by the complex.

Thus, should always be lower? Not necessarily. It really depends on the context of your system. However, if not much is known of your system, then you can infer some possible explanations, as I mentioned.

Best regards,

Bruno

There is no different in your results between your ligand and the reference complex;

It is not necessary to compare your results with the reference complex. you are studying the stability of your complex (ligand-target), if you have got low RMSD or the the RMSD keep going up during the simulation.

Govinda Rao Dabburu

I'm not sure if you're referring to protein-ligand RMSD from MD or clusters from docking, but regardless, you could always visualize your structure files. In most cases of high RMSD, you will notice your ligand off-target (or reasonably far) and hence derive a conclusion.