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Updated: Jun 6, 2026

Measuring Biomolecular DSC Profiles with Thermolabile Ligands to Rapidly Characterize Folding and Binding Interactions
Published on: November 21, 2017
Dissecting the molecular determinants of ligand-binding-induced macromolecular switching using thermodynamic cycles
Martin T J Smith1, Duncan W S Mackenzie, Elizabeth M Meiering
1Guelph-Waterloo Centre for Graduate Work in Chemistry and Biochemistry, Department of Chemistry, University of Waterloo, 200 University Avenue, Waterloo, Ontario, Canada.
Abstract:
The energetic networks that govern regulated switching processes in macromolecules are poorly understood at a molecular level. We illustrate a general methodology that uses thermodynamic cycles to measure the coupling energetics between specific groups in a macromolecule and ligand-binding-induced macromolecular switching. The approach is applied to new and published thermodynamic stability and/or binding data not previously analyzed in this way, for a wide range of switching systems, including H+ or Ca²+-binding-induced myristoyl switching, ion or peptide-binding-induced conformational switching in various proteins and small molecule binding to a ribo-switch. The results show how this powerful approach can be used to identify and dissect the molecular determinants of switching in macromolecules.
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