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

In this paper we analyze published data on Delta H and Delta S values for t he DNA melting transition under various conditions. We show that there is a significant heat capacity increase ac, associated with DNA melting, in the range of 40-100 cal/mol K per base pair. This is larger than the transitio n entropy per base pair, Delta S degrees approximate to 25 cal/mol K. The r atio of Delta C-p/Delta degrees S determines the importance of heat capacit y effects on melting. For DNA this ratio is 2-4, larger than for many prote ins. We discuss how Delta C-p values can be extracted from experimental dat a on the dependence of Delta H and Delta S 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 depen dence of T-m on salt, electrostatics alone cannot explain the accompanying strong variation of Delta H and Delta S. While T-m is only weakly affected by Delta C-p, its dependence on one parameter (e.g., salt) as a function of another (e.g., DNA composition) is determined by Delta C-p. We show how th is accounts for the stronger stabilization of AT relative to GC base pairs with increasing ionic strength. We analyze the source of discrepancies in D elta H as determined by calorimetry and van't Hoff analysis and discuss way s of analyzing data that yield valid van't Hoff Delta H. Finally, we define a standard state for DNA melting, the temperature at which thermal contrib utions to Delta H and Delta S vanish, by analyzing experimental data over a broad range of stabilities.