Entropy-enthalpy compensation may be a useful interpretation tool for complex systems like protein-DNA complexes: An appeal to experimentalists

Abstract

In various chemical systems enthalpy-entropy compensation (EEC) is a wellknown 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.In the recent papers [1,2], the effects of genetic variants of TGACGTCA DNA binding motif, as well as of successive C-terminal truncation of leucine zippers, on the energetics of DNA binding to bZIP domains in Jun transcription factor have been studied using analytical laser scattering in combination with isothermal titration calorimetry. The systematical study [1] reveals that the bZIP domains exhibit differential energetics in binding to DNA fragments containing single nucleotide variations within the TGACGTCA canonical motif. Further, it has been persuasively shown [2] that the successive C-terminal truncation of residues leading up to each signature leucine significantly compromises the binding of bZIP domains to the canonical DNA motif. Moreover, in these both works a valid enthalpy-entropy compensation (EEC) has been revealed. Fig. 1 and its legend for the details of the regression analysis), with the coefficients: a = 305 K, b = -7.48 kcal/mol. Thus, on the S-T diagram of the corresponding "imaginary/hidden Carnot cycle", the temperature is slightly going up from room temperature 298.15 K to 305 K, whereas the pertinent entropy difference is DS = b/a = -24.51 cal/(mol K). error for the intercept is 0.658, the correlation coefficient is 0.992, its standard error is 0.026, residual sum of squares is 2.429. According to the conventional residual-based diagnostic tools, there is little evidence against the normality of the data set, whereas according to the F-statistic, there are little or no real evidences against the linearity of the plot. Therefore, we obtain a valid linear regression, with the slope greater or equal to 1.Similarly, by fitting the relevant da...

Hydrogen Bonding in Liquid Water and in the Hydration Shell of Salts

“…[78] Starikov and NordØn showed that the EEC was ar eal and valid phenomenon that couldb ee xplained by using classical thermodynamics and proved by using exact statisticalt reatment. [79][80][81][82] According to Starikov and NordØn, the EEC effect could be expressed by Equation (7):…”

Entropy–enthalpy compensation of biomolecular systems in aqueous phase: a dry perspective

“…Methodical modifications of the sequence of the DNA binding revealed EEC with Δ G C = −3.15 kJ/mol (18). In contrast, systematic alterations in the length of the binding protein (bZIP domain) resulted in an EEC signature with a compensation temperature of 291 K and Δ G C = −37.4 kJ/mol.…”

“…Another intriguing idea has been advanced in several papers by Starikov and Nordén, who rationalize EEC data in terms of a micro-phase transition (MPT) (14;18). Starikov and Nordén explained that modifications of the nucleotide sequence of the DNA binding site corresponded to an “imaginary artificial heat pump,” whereas the changes of the binding polypeptide chain, which also involved changes in electrostatics, represented a “imaginary artificial refrigerator,” accounting for an equivalent Carnot cycle of the MPT (18).…”

“…Starikov and Nordén explained that modifications of the nucleotide sequence of the DNA binding site corresponded to an “imaginary artificial heat pump,” whereas the changes of the binding polypeptide chain, which also involved changes in electrostatics, represented a “imaginary artificial refrigerator,” accounting for an equivalent Carnot cycle of the MPT (18). In this respect it is interesting that both the eEEC and MEE models lead to entropy changes that are proportional to the enthalpy change.…”

Bayesian Statistical Mechanics: Entropy-Enthalpy Compensation and Universal Equation of State at the Tip of Pen

“…Figure 1 depicts typical behavior of entropy and enthalpy vs. temperature, and one can immediately recognize the convergent behavior of the both up to the value of x = 1, after which the graphs diverge. Hence, it is throughout possible to interpret this as an enthalpy-entropy compensation (EEC), whereas x = 1, that is, T = T ref defines the so-called "enthalpy-entropy compensation temperature" T c , that is, T ref ≡ T c (see e.g., [43][44][45][46][47][48][49][50][51][52] and the references therein).…”