ENTHALPY-ENTROPY COMPENSATION IN DNA MELTING THERMODYNAMICS

We investigate enthalpy-entropy compensation for melting of nearest-neighbor doublets in DNA. Eased on data for 10 normal doublets and for doublets containing a mispaired or analog base, the correlation of Delta S degrees with Delta H degrees follows a rectangular hyperbola. Doublet melting temperature relates linearly to Delta H degrees by T-m = T-o + Delta H degrees/a, where T-o approximate to 273 K and a approximate to 80 cal/mol-K. Thus T-m is proportional to Delta H degrees + aT(o) rather than to Delta H degrees alone as previously thought by assuming Delta S degrees to be constant. The term aT(o) approximate to 21.8 kcal/mol may reflect a constant enthalpy change in solvent accompanying the DNA enthalpy change for doublet melting and is roughly equivalent to breaking four H-bonds between water molecules for each melted doublet. The solvent entropy change (aT(o)/T-m) declines with increasing T-m, while the DNA entropy change (Delta H degrees/T-m) rises, so the combined DNA + solvent entropy change stays constant at 80 cal/K/mol of doublet. If such constancy in DNA + solvent entropy changes also holds for enzyme clefts as ''solvent,'' then free energy differences for competing correct and incorrect base pairs in polymerase clefts may be as large as enthalpy differences and possibly sufficient to account for DNA polymerase accuracy. The hyperbolic relationship between Delta S degrees and Delta H degrees observed in 1 M salt can be used to evaluate Delta H degrees and Delta S degrees from T-m at lower, physiologically relevant, salt concentrations.