FOR THE RECORD
Entropy—enthalpy compensation: Fact or artifact?
Article first published online: 31 DEC 2008
Copyright © 2001 The Protein Society
Volume 10, Issue 3, pages 661–667, March 2001
How to Cite
Sharp, K. (2001), Entropy—enthalpy compensation: Fact or artifact?. Protein Science, 10: 661–667. doi: 10.1110/ps.37801
- Issue published online: 31 DEC 2008
- Article first published online: 31 DEC 2008
- Manuscript Accepted: 15 DEC 2000
- Manuscript Revised: 6 DEC 2000
- Manuscript Received: 6 SEP 2000
- enthalpy compensation;
- protein thermodynamics
The phenomenon of entropy–enthalpy (S-H) compensation is widely invoked as an explanatory principle in thermodynamic analyses of proteins, ligands, and nucleic acids. It has been suggested that this compensation is an intrinsic property of either complex, fluctuating, or aqueous systems. The questions examined here are whether the observed compensation is extra-thermodynamic (i.e., reflects anything more than the well-known laws of statistical thermodynamics) and if so, what does it reveal about the system? Compensation is rather variably defined in the literature and different usages are discussed. The most precise and interesting one, which is considered here, is a linear relationship between ΔH and ΔS for some series of perturbations or changes in experimental variable. Some recent thermodynamic data on proteins purporting to show compensation is analyzed and shown to be better explained by other causes. A general statistical mechanical model of a complex system is analyzed to explore whether and under what conditions extra-thermodynamic compensation can occur and what it reveals about the system. This model shows that the most likely behavior to be seen is linear S-H compensation over a rather limited range of perturbations with a compensation temperature Tc = dΔH/dΔS within 20% of the experimental temperature. This behavior is insensitive to the details of the model, thus revealing little extra-thermodynamic or causal information about the system. In addition, it will likely be difficult to distinguish this from more trivial forms of compensation in real experimental systems.