ReviewEuropean biophysics journal : EBJ2017
Enthalpy-entropy compensation: the role of solvation.
Review in European biophysics journal : EBJ, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed.
- Enthalpy-Entropy Trade-Off Underlies Geometric Isomer Selectivity in Histamine HACS medicinal chemistry letters · 2026Article
- Anion-π interaction-induced phase separation as a prebiotic pathway to oxygenation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Solubility of Sulfamethazine in Acetonitrile-Ethanol Cosolvent Mixtures: Thermodynamic Analysis and Mathematical Modeling.Molecules (Basel, Switzerland) · 2025Article
- Allostery without Conformational Change: A Native Mass Spectrometry Perspective.The journal of physical chemistry. B · 2025Article
- Thermodynamics of Molecular Transport Through a Nanochannel: Evidence of Energy-Entropy Compensation.International journal of molecular sciences · 2025Article
- The Transcription Machinery and the Driving Force of the Transcriptional Molecular Condensate: The Role of Phosphates.Current issues in molecular biology · 2025Article
- On Enthalpy-Entropy Compensation Characterizing Processes in Aqueous Solution.Entropy (Basel, Switzerland) · 2025Review
- Structure and Stabilities of Solution and Gas Phase Protein Complexes.Journal of the American Society for Mass Spectrometry · 2024Article
- Complexity associated with caprylate binding to bovine serum albumin: Dimerization, allostery, and variance between the change in free energy and enthalpy of binding.Protein science : a publication of the Protein Society · 2024Article
- The Role of Medium Polarity in the Efficiency of Albumin Binding with Hydrophobic Ligands: Experimental Studies and a Molecular Dynamics Investigation.International journal of molecular sciences · 2024Article
- Temperature-Dependent TrimethylamineThe journal of physical chemistry. B · 2024Article
- Keeping the Distance: Activity Control in Solid-Supported Sucrose Phosphorylase by a Rigid α-Helical Linker of Tunable Spacer Length.ACS catalysis · 2024Article
- Driving Forces in the Formation of Biocondensates of Highly Charged Proteins: A Thermodynamic Analysis of the Binary Complex Formation.Biomolecules · 2024Article
- Extreme enthalpy‒entropy compensation in the dimerization of small solutes in aqueous solution.European biophysics journal : EBJ · 2024Review
- Fluctuations in Medium Viscosity May Affect the Stability of the CAG Tract in theBiomedicines · 2024Article
- Polymers for Disrupting Protein-Protein Interactions: Where Are We and Where Should We Be?Biomacromolecules · 2024Review
- A role for conformational changes in enzyme catalysis.Biophysical journal · 2024Article
- Using Implicit-Solvent Potentials to Extract Water Contributions to Enthalpy-Entropy Compensation in Biomolecular Associations.The journal of physical chemistry. B · 2023Article
- Entropic Origin of Ionic Interactions in Polar Solvents.The journal of physical chemistry. B · 2023Article
- Dissecting the Thermodynamics of ATP Binding to GroEL One Nucleotide at a Time.ACS central science · 2023Article
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Structural modifications to interacting systems frequently lead to changes in both the enthalpy (heat) and entropy of the process that compensate each other, so that the Gibbs free energy is little changed: a major barrier to the development of lead compounds in drug discovery. The conventional explanation for such enthalpy-entropy compensation (EEC) is that tighter contacts lead to a more negative enthalpy but increased molecular constraints, i.e., a compensating conformational entropy reduction. Changes in solvation can also contribute to EEC but this contribution is infrequently discussed. We review long-established and recent cases of EEC and conclude that the large fluctuations in enthalpy and entropy observed are too great to be a result of only conformational changes and must result, to a considerable degree, from variations in the amounts of water immobilized or released on forming complexes. Two systems exhibiting EEC show a correlation between calorimetric entropies and local mobilities, interpreted to mean conformational control of the binding entropy/free energy. However, a substantial contribution from solvation gives the same effect, as a consequence of a structural link between the amount of bound water and the protein flexibility. Only by assuming substantial changes in solvation-an intrinsically compensatory process-can a more complete understanding of EEC be obtained. Faced with such large, and compensating, changes in the enthalpies and entropies of binding, the best approach to engineering elevated affinities must be through the addition of ionic links, as they generate increased entropy without affecting the enthalpy.
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