Cross linking can give you a rough idea about the distance between the two residues. But due to the limitation of number of residues that can be cross linked, it would not give you a detailed view of the interacting surface(s).

This paper concerns investigation of a protein-protein interaction by crosslinking and mass spectrometry.

Hi Abir, if you have your interacting proteins already purified, I would suggest using a zero-length crosslinker like EDC.

Hi Dr Stein,

I have two purified proteins. protein 1 is 30 kDa and protein 2 is 40 kDa.

Hi Abir, if you have the purified proteins that are interacting, you can use gel filtration of a mixture of protein 1 + protein 2. If they interact you should see 3 peaks, 30K, 40K and 70K (1+2).