ITC. MST requires additional tagging with fluorophore and needs to optimize the capillary types. SPR relies on immobilization (need to buy sensor chips) and expensive.

Fluorescence anisotropy is another in-solution method (https://www.ncbi.nlm.nih.gov/pubmed/27805607) . The expected Kd plays an important role in which methods are suitable. For KD determination, you have to work at different subsaturating concentrations. For very high affinities (low nM to pM), sensitivity may become a problem, while for very low affinities, the high protein concentrations required may influence the viscosity of the solution.

If your two proteins are easily to get or have high yield, you may use ITC as it needn't extra labelling dye, capillaries or sensor chip which are needed in MST or SPR. While if your proteins are precious, you may try MST as it will save much samples also time when compared to ITC.

A yeast two hybrid system would be useful to analyse potential protein interaction.

If the hexamer is in equilibrium, ITC will not help. You will indeed measure the heat of the interaction of the six monomers forming the oligomer and the smaller protein interacting with the hexamer (or monomers of the hexamer?). The results will be non conclusive. If you think your 17 kDa protein is interacting with the monomers, it might be worth immobilising them on a chip in SPR or BLI.