Translational Entropy and DNA Duplex Stability

Abstract

Investigation of folding/unfolding DNA duplexes of various size and composition by superprecise calorimetry has revised several long-held beliefs concerning the forces responsible for the formation of the double helix. It was established that: 1) the enthalpy and the entropy of duplex unfolding are temperature dependent, increasing with temperature rise and having the same heat capacity increment for CG and AT pairs; 2) the enthalpy of AT melting is greater than that of the CG pair, so the stabilizing effect of the CG pair in comparison with AT results not from its larger enthalpic contribution (as expected from its extra hydrogen bond), but from the larger entropic contribution of the AT pair that results from its ability to fix ordered water in the minor groove and release it upon duplex unfolding; 3) the translation entropy, resulting from the appearance of a new kinetic unit on duplex dissociation, determines the dependence of duplex stability on its length and its concentration (it is an order-of-magnitude smaller than predicted from the statistical mechanics of gases and is fully expressed by the stoichiometric correction term); 4) changes in duplex stability on reshuffling the sequence (the "nearest-neighbor effect") result from the immobilized water molecules fixed by AT pairs in the minor groove; and 5) the evaluated thermodynamic components permit a quantitative expression of DNA duplex stability.

Modeling Structure, Stability, and Flexibility of Double-Stranded RNAs in Salt Solutions

“…The stability of dsRNAs generally depends on strand concentration due to the contribution of translation entropy of melted ssRNA chains (64). However, for dsRNA with low strand concentrations (e.g., 0.1 mM in experiments), a very long simulation time is generally required to reach equilibrium for the dsRNA system.…”

Modeling structure, stability and flexibility of double-stranded RNAs in salt solutions

“…The stability of dsRNAs generally depends on strand concentration due to the contribution of translation entropy of melted ssRNA chains (60). However, for a dsRNA with low strand concentrations (e.g., 0.1 mM in experiments), a very long simulation time is generally required to reach equilibrium for the dsRNA system.…”

Forces maintaining the DNA double helix

“…The magnitude of the translational entropy was for a long time a matter of heated theoretical discussion: proposed values scattered from 230 J/(K mol) (Finkelstein and Janin 1989 ) to 400 J/(K mol) (Tidor and Karplus 1994 ). However, using a Nano-DSC it can be determined by measuring the unfolding entropies of all-CG DNA duplexes of various sizes and concentrations (Privalov and Crane-Robinson 2018b ). It was found that the translation entropy increase on DNA duplex unfolding is perfectly described by the simple equation: as originally predicted by Gurney ( 1953 ), but widely rejected as being physically inconsistent.…”

“… To minimize the near-neighbor effect, DNA duplexes containing at least 12 base pair of contiguous CG or AT sequences were chosen (Vaitiekunas et al 2015 ). All data have been corrected for the translation entropy to exclude the effects of duplex concentration (Privalov and Crane-Robinson 2018b ). These two precautions permitted a significant decrease in the error in estimating the thermodynamic contributions of the base pairs …”

“…Comparison of these values shows that the duplex stabilizing effect of the CG base pair is larger than that of the AT, not because its enthalpic contribution is larger but because its entropic contribution is smaller (Vaitiekunas et al 2015 ; Privalov and Crane-Robinson 2018b ). The question is then: why are the entropic and also enthalpic contributions of the AT base pair larger than that for CG pairs?…”