Entropy-Enthalpy Compensation May Be a Useful Interpretation Tool for Complex Systems Like Protein-DNA Complexes: An Appeal to Experimentalists

TL;DR

This paper explores the physical basis of enthalpy-entropy compensation (EEC) in complex systems like protein-DNA interactions, proposing that hidden micro-phase transitions and correlation analysis can clarify its underlying mechanisms.

Contribution

It introduces a new perspective on EEC using correlation and factor analysis, suggesting a link to micro-phase transitions in complex biological and chemical systems.

Findings

EEC may be explained by hidden micro-phase transitions.

Correlation analysis can reveal underlying factors in EEC.

EEC is relevant to hydration, folding, and conformational changes in biomolecules.

Abstract

In various chemical systems enthalpy-entropy compensation (EEC) is a well-known rule of behavior, although the physical roots of it are still not completely understood. It has been frequently questioned whether EEC is a truly physical phenomenon or a coincidence due to trivial mathematical connections between statistical-mechanical parameters - or even simpler: A phantom effect resulting from the misinterpretation of experimental data. Here, we review EEC from a new standpoint using the notion of correlation which is essential for the method of factor analysis, but is not conventional in physics and chemistry. We conclude that the EEC may be rationalized in terms of hidden (not directly measurable with the help of the current experimental set-up) but physically real factors, implying a Carnot-cycle model in which a micro-phase transition (MPT) plays a crucial role. Examples of such MPTs underlying physically valid EEC should be typically cooperative processes in supramolecular aggregates, like changes of structured water at hydrophobic surfaces, conformational transitions upon ligand-biopolymer binding, and so on, so forth. The MPT notion could help rationalize the occurrence of EEC in connection with hydration and folding of proteins,enzymatic reactions, functioning of molecular motors, DNA de- and rehybridization, as well as similar phenomena.