Summary
Isothermal titration [Holdgate (BioTechniques 31:164–184, 2001); Ward and Holdgate (Prog. Med. Chem. 38:309–376, 2001); O’Brien et al. (2001) Isothermal titration calorimetry of biomolecules. In: Harding, S. E. and Chowdhry, B. Z. (eds.), Protein–Ligand Interactions: Hydrodynamics and Calorimetry, A Practical Approach. Oxford University Press, Oxford, UK] and differential scanning calorimetry [Jelesarov and Bosshard (J. Mol. Recognit. 12:3–18, 1999); Privalov and Dragan (Biophys. Chem. 126:16–24, 2007); Cooper et al. (2001) Differential scanning microcalorimetry. In: Harding, S. E. and Chowdhry, B. Z. (eds.), Protein-Ligand Interactions: Hydrodynamics and Calorimetry, A Practical Approach. Oxford University Press, Oxford, UK] are valuable tools for characterising protein targets, and their interactions with ligands, during the drug discovery process. The parameters obtained from these techniques: ▵ΔH, ▵ΔG, ▵ΔS, and ▵ΔC p, are properties of the entire system studied and may be composed of many contributions, including the binding reaction itself, conformational changes of the protein and/or ligand during complexation, changes in solvent organisation or other equilibria linked to the binding process. Dissecting and understanding these components, and how they contribute to binding interactions, is a critical step in the ability to design ligands that have high binding affinity for the target protein.
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The author would like to thank Dr. Gareth Davies for critically reading the manuscript.
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Holdgate, G. (2009). Isothermal Titration Calorimetry and Differential Scanning Calorimetry. In: Roque, A. (eds) Ligand-Macromolecular Interactions in Drug Discovery. Methods in Molecular Biology, vol 572. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-244-5_7
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