Journal of Thermal Analysis and Calorimetry

, Volume 138, Issue 5, pp 3229–3248 | Cite as

Handling complexity in biological interactions

Allostery and cooperativity in proteins
  • Sonia Vega
  • Olga AbianEmail author
  • Adrian Velazquez-CampoyEmail author


Biological processes rely on interactions between many binding partners. Binding results in the modulation of the conformational landscape of the interacting molecules, a phenomenon rooted in folding and binding cooperativity underlying the allosteric functional regulation of biomacromolecules. The conformational equilibrium of a protein and the binding equilibria of different interacting and cooperative ligands are coupled giving rise to a complex scenario in which protein function can be finely tuned and modulated. Binding cooperativity and allostery add additional levels of complexity in protein function regulation. Here we will review some important concepts associated with binding, cooperativity and allostery in protein interactions, illustrated with several representative protein-dependent biological systems related to drug discovery and physiological mechanisms characterization and studied by isothermal titration calorimetry.


Allostery Interaction cooperativity Ligand binding Binding polynomial Conformational landscape Biochemical linkage 



This work was supported by Miguel Servet Program from Instituto de Salud Carlos III (CPII13/00017 to OA); Fondo de Investigaciones Sanitarias from Instituto de Salud Carlos III, and European Union (ERDF/ESF, ‘Investing in your future’) (PI15/00663 and PI18/00349 to OA); Spanish Ministry of Economy and Competitiveness (BFU2016-78232-P to AVC); Diputación General de Aragón (Protein Targets and Bioactive Compounds Group E45_17R to AVC, and Digestive Pathology Group B25_17R to OA); and Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Akadémiai Kiadó, Budapest, Hungary 2019

Authors and Affiliations

  1. 1.Institute of Biocomputation and Physics of Complex Systems (BIFI), Joint Units IQFR-CSIC-BIFI, and GBsC-CSIC-BIFIUniversidad de ZaragozaZaragozaSpain
  2. 2.Departamento de Bioquímica y Biología Molecular y CelularUniversidad de ZaragozaZaragozaSpain
  3. 3.Aragon Institute for Health Research (IIS Aragon)ZaragozaSpain
  4. 4.Biomedical Research Networking Centre for Liver and Digestive Diseases (CIBERehd)MadridSpain
  5. 5.Aragon Health Sciences Institute (IACS)ZaragozaSpain
  6. 6.ARAID FoundationGovernment of AragonZaragozaSpain

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