A Simple Model for Determining Affinity from Irreversible Thermal Shifts
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Thermal denaturation (Tm) data are easy to obtain; it is a technique that is used by both small labs and large-scale industrial organizations. The link between ligand affinity (K ) and ΔTm is understood for reversible denaturation; however, there is a gap in our understanding of how to quantitatively interpret ΔTm for the many proteins that irreversibly denature. To better understand the origin, and extent of applicability, of a K to ΔTm correlate, we define equations relating K and ΔTm for irreversible protein unfolding, which we test with computational models and experimental data. These results suggest a general relationship exists between K and ΔTm for irreversible denaturation.
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