Functional Application Areas

DSC & Protein-Ligand Interactions

DSC is primarily used to characterize stability and folding.  It can also be used to study binding interactions between proteins and small molecules, drugs, and other proteins. When a small molecule ligand preferentially binds to the native form of a protein, the ligand stabilizes the protein and the T_m of the protein-ligand complex is higher than that of the protein in the absence of ligand.  If the ligand preferentially binds to the denatured protein, the T_m decreases in the presence of the ligand.  DSC is used to measure the binding constants from T_m shifts due to drug (or other small molecule) binding to a protein (Figure 1). The binding constant of the ligand can be estimated from the T_ms in the presence and absence of ligand, as long as the concentration of ligand in the DSC cell is known   This method can estimate binding constants up to 10²⁰ M^-1.  It can be used for ligands with ultratight binding constants that cannot be measured by other methods, as well as a screening assay for drug discovery.

Figure 1. The effect of adding different anionic inhibitors to Ribonuclease A (0.09mM).

Reference List

DSC – Protein-Small Molecule Interactions Reference List

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