Heat capacity effects on the melting of DNA. 1. General aspects

In this paper we analyze published data on DeltaH and DeltaS values for the DNA melting transition under various conditions. We show that there is a significant heat capacity increase DeltaC(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, DeltaS(0) approximately 25 cal/mol K. The ratio of DeltaC(p)/DeltaS(0) determines the importance of heat capacity effects on melting. For DNA this ratio is 2-4, larger than for many proteins. We discuss how DeltaC(p) values can be extracted from experimental data on the dependence of DeltaH and DeltaS 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 DeltaH and DeltaS. While T(m) is only weakly affected by DeltaC(p), its dependence on one parameter (e.g., salt) as a function of another (e.g., DNA composition) is determined by DeltaC(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 DeltaH as determined by calorimetry and van't Hoff analysis and discuss ways of analyzing data that yield valid van't Hoff DeltaH. Finally, we define a standard state for DNA melting, the temperature at which thermal contributions to DeltaH and DeltaS vanish, by analyzing experimental data over a broad range of stabilities.