Searching for quantitative entropy‐enthalpy compensation among protein variants

Abstract

Entropy-enthalpy (SH) compensation occurs when a small change in DeltaG is caused by large, and nearly compensatory, changes in DeltaH and DeltaS. It is considered a ubiquitous property of reactions in water. Because water is intimately involved in protein stability, SH compensation among protein variants, if it exists, could lead to important knowledge about protein-water interactions. In light of recent theoretical work on SH compensation, we gathered thermodynamic data for >200 protein variants to seek evidence for the simplest quantitative model of SH compensation (i.e., The van't Hoff denaturation enthalpy divided by the van't Hoff denaturation entropy is a constant). We conclude that either the data are insufficient to support the idea that quantitative SH compensation is a general feature of variant proteins or that such compensation does not exist. This study reinforces the idea that DeltaH-versus-DeltaS plots should not be used to provide evidence for SH compensation.