Heat Capacity Effects on the Melting of DNA. 1. General Aspects

AbstractIn this paper we analyze published data on ΔH and ΔS values for the DNA melting transition under various conditions. We show that there is a significant heat capacity increase ΔCp associated with DNA melting, in the range of 40–100cal/molK per base pair. This is larger than the transition entropy per base pair, ΔS0≈25cal/molK. The ratio of ΔCp/ΔS0 determines the importance of heat capacity effects on melting. For DNA this ratio is 2–4, larger than for many proteins. We discuss how ΔCp values can be extracted from experimental data on the dependence of ΔH and ΔS on the melting temperature Tm. We consider studies of DNA melting as a function of ionic strength and show that while polyelectrolyte theory provides a good description of the dependence of Tm on salt, electrostatics alone cannot explain the accompanying strong variation of ΔH and ΔS. While Tm is only weakly affected by ΔCp, its dependence on one parameter (e.g., salt) as a function of another (e.g., DNA composition) is determined by ΔCp. We show how this accounts for the stronger stabilization of AT relative to GC base pairs with increasing ionic strength. We analyze the source of discrepancies in ΔH as determined by calorimetry and van’t Hoff analysis and discuss ways of analyzing data that yield valid van’t Hoff ΔH. Finally, we define a standard state for DNA melting, the temperature at which thermal contributions to ΔH and ΔS vanish, by analyzing experimental data over a broad range of stabilities