You can try IR technique.

In principle, any technique that can distinguish the protein in its free state from its complexed state could allow you to quantify the binding equilibrium constant (Kb), and then the binding free energy. Then, you can obtain Kb at different temperatures and then estimate the binding enthalpy through the van't Hoff 's method. Spectroscopic methods such as UV-Vis Differential Absorption or Fluorescence could be useful in this respect.

You can try to use XRD if the interaction leads to at an arrangement of protein and ligand.

The ITC and DSC are the best technique for interaction study between a protein and a small ligand for get some important biothermodynamic and energetic parameters. These parameter can distinguish and comparing stability of conjugate product to other. However some of easy and enough accurate spectroscopic methods such as CD, UV, Fluorescence and .. could be useful for achieve the structural changes in interaction study.

Surface plasmon resonance is frequently used (e.g. BIACore). You have to immobilize the protein on the sensor chip surface, then flow the ligand over it and measure the change in mass bound to the surface optically. There are lots of other methods. Sometimes, you can measure binding of the ligand to the protein by changes in the protein's tryptophan fluorescence intensity or emission wavelength (correcting for any interference from the absorbance or fluorescence of the ligand using N-acetyltryptophanamide as a surrogate for the protein). The Hummel & Dreyer method is useful if you have an FPLC or HPLC with gel filtration. You vary the concentration of the ligand in the elution buffer, inject some of the protein, and measure the area of the "vacancy peak" (reduced compound absorbance) to get the amount of ligand bound. You could use equilibrium dialysis. ThermaFluor is a method that measures ligand binding by an increase in the melting temperature of the protein due to stabilization (like DSC).