title: Dissecting the molecular determinants of ligand-binding-induced macromolecular switching using thermodynamic cycles.
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.
authors.affiliation: Guelph-Waterloo Centre for Graduate Work in Chemistry and Biochemistry, Department of Chemistry, University of Waterloo, 200 University Avenue, Waterloo, Ontario, Canada.
authors.forename: Martin T J
authors.initials: MT
authors.lastname: Smith
authors.forename: Duncan W S
authors.initials: DW
authors.lastname: Mackenzie
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Meiering
mesh_terms: D001665:Binding Sites; D008024:Ligands; D009227:Myristic Acids / Q000737:chemistry; D011485:Protein Binding; D055550:Protein Stability; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D008024:Ligands; D009227:Myristic Acids; D011506:Proteins