A method for measuring a binding property between a compound and a target macromolecule, comprising: (a) preparing a fluid mixture comprising (i) a chimeric molecule comprising a target macromolecule subject to denaturation linked to a labeling peptide and (ii) a compound being measured for binding to the target macromolecule; wherein the target macromolecule has a secondary or tertiary structure that can be denatured, and the labeling peptide has no secondary structure, and has no effect on the stability of the target macromolecule, wherein the labeling peptide is an enzyme fragment; (b) incubating the fluid mixture of step (a) under conditions permitting binding of said compound to target macromolecules in the mixture; (c) treating the fluid mixture of step (b) under conditions that cause a differential denaturation between chimeric molecules bound to the compound and chimeric molecules not bound to the compound; and (d) generating a signal from chimeric molecules subjected to said differential denaturation in step (c), by adding to the mixture a second label that reacts with the labeling peptide in the chimeric molecule, wherein the second label is a complementary enzyme fragment which can combine with the labeling peptide to create an active enzyme, wherein, (e) the signal in step (d) is detected and indicates a binding property between the compound and the target macromolecule, wherein detecting a signal indicates a differential between (i) denatured and (ii) non-denatured target macromolecules and thereby a differential between target macromolecules not bound to the compound and target macromolecules bound to the compound, respectively, wherein the differential is because when the compound does not bind to the target macromolecule then the target macromolecule is denatured rendering the labelling peptide inaccessible for complementation, whereas when the compound does bind to the target macromolecule the target macromolecule is protected from denaturation in its native form enabling detection of the binding by enzyme complementation between the labeling peptide and second label. (a) preparing a fluid mixture comprising (i) a chimeric molecule comprising a target macromolecule subject to denaturation linked to a labeling peptide and (ii) a compound being measured for binding to the target macromolecule; wherein the target macromolecule has a secondary or tertiary structure that can be denatured, and the labeling peptide has no secondary structure, and has no effect on the stability of the target macromolecule, wherein the labeling peptide is an enzyme fragment; (b) incubating the fluid mixture of step (a) under conditions permitting binding of said compound to target macromolecules in the mixture; (c) treating the fluid mixture of step (b) under conditions that cause a differential denaturation between chimeric molecules bound to the compound and chimeric molecules not bound to the compound; and (d) generating a signal from chimeric molecules subjected to said differential denaturation in step (c), by adding to the mixture a second label that reacts with the labeling peptide in the chimeric molecule, wherein the second label is a complementary enzyme fragment which can combine with the labeling peptide to create an active enzyme, wherein, (e) the signal in step (d) is detected and indicates a binding property between the compound and the target macromolecule, wherein detecting a signal indicates a differential between (i) denatured and (ii) non-denatured target macromolecules and thereby a differential between target macromolecules not bound to the compound and target macromolecules bound to the compound, respectively, wherein the differential is because when the compound does not bind to the target macromolecule then the target macromolecule is denatured rendering the labelling peptide inaccessible for complementation, whereas when the compound does bind to the target macromolecule the target macromolecule is protected from denaturation in its native form enabling detection of the binding by enzyme complementation between the labeling peptide and second label.