In 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 ΔC(p) associated with DNA melting, in the range of 40-100 cal/mol K per base pair. This is larger than the transition entropy per base pair, ΔS0 ≃ 25 cal/mol K. The ratio of ΔC(p)/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 ΔC(p) values can be extracted from experimental data on the dependence of ΔH and ΔS on the melting temperature T(m). 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 T(m) on salt, electrostatics alone cannot explain the accompanying strong variation of ΔH and ΔS. While T(m) is only weakly affected by ΔC(p), its dependence on one parameter (e.g., salt) as a function of another (e.g., DNA composition) is determined by ΔC(p). 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.
Bibliographical noteFunding Information:
This research was supported in part by National Institutes of Health research grant GM28093.