You can use different methods depending on the protein and the ligand you have.

if there is lot of protein availiable use ITC if not but you got Tyr or Trp in the binding site you could use fluorescence titration experiment. both can be used for Ks determination. For specific interction (H-bonds, etc) you will need NMR X-ray crystallography, CD.

If the bindi ng is tight enough, it can also be determined by gel filtration.

I am pretty sure that you can measure the binding efficiency of your protein and its ligand; the rest of it really depends on what your protein does.

Is there any biphysical methods available that can be used to determine the interaction, without involving any type of crystallization step and involvement of tagging??

Yes, you can use ITC. It is label free and a solution method and gives H, S, affinity and stoichiometry values in one single experiment. Only downside is you may need more protein than say a fluorescence based method.

But for ITC, i believe we need a specialized instrument to mesaure the heat energy released..

yes you need a specialized calorimeter. Are you looking for a qualitative or quantitative method for your interaction?

But in case i need to find out the possible physical interaction between the protein and the ligand, will the above methods suffice my cause?

If you are working with purified proteins, above mentioned biophysical methods probe the physical interaction. You can also add SPR and Analytical ultracentrifuge to the list.

I know its too late to reply for this question, but still I think it may be useful now or in future. follow this link

http://www.labome.com/method/Protein-Receptor-Ligand-Interaction-Binding-Assays.html