Control experiments ideally use a system that is very similar to the one under investigation. Some ideas for control experiments are given here:

• Protein: Mutant, truncation, homolog; Fluorescent fusion proteins or tag alone (for example, GST)
• Nucleic acid: Similar but different sequence
• Ion: Different ion of the same charge and similar size
• Photobleaching control experiment: Using Fluorophores alone as Target to distinguish between a non-specific, ligand-induced, chemical effect on the fluorophore and an effect caused by an interaction between the target and Ligand.
• His-tag labeling: The NanoTemper Technologies His-tag Protein Labeling kits provide a His6-control peptide which can be used instead of the His-tagged target molecule to control for unspecific interaction of ligand molecules with the RED-tris-NTA dye.