There are many kits available for attaching small organic fluorophores to purified proteins. For an example of one vendor, see the link below.

https://www.thermofisher.com/us/en/home/life-science/protein-biology/protein-labeling-crosslinking/fluorescent-protein-labeling.html

Most of these kits attach the label non-specifically to surface-exposed lysine residues and the N-terminus, if it is free. There is no guarantee that this labeling won't affect the interaction, since fluorophores are bulky molecules, and since the lysine residues may be involved in the interaction.If there are multiple surface-exposed Lys residues, you can't control where the label will go. Try to keep the labeling stoichiometry low (~1).

If you can arrange it, a more specific labeling approach is to start with a protein containing only one surface exposed Cys residue, preferable somewhere out of the way of the part that interacts with the other protein. Cys can be labeled with high specificity using maleimide or alkyl halide chemistry.

Choose a fluorophore that has the right excitation and emission wavelengths for detection by your instrument.

Adam B Shapiro Dr. Shapiro, Thank you so very much for your insightful suggestions. I am looking on the product you suggested. I found that the labeling fluorophore (Alexa 488) has several options. Can I go for Cadaverine labeling which is used to label the carbonyl group (=CO) of protein ?

Thank you

With kind regard

Prem

That's one way to do it. It will modify carboxylic acid side chains in the presence of a carbodiimide. It's more common to do lysine labeling with a succinimidyl ester derivative of the fluorophore.