Hydration heat capacity of nucleic acid constituents determined from the random network model

The heat capacities of hydration (dCp) of the five nucleic acid bases A, G, C, T, and U, the sugars ribose and deoxyribose, and the phosphate backbone were determined using Monte Carlo simulations and the random network model. Solute-induced changes in the mean length and root mean square angle of hydrogen bonds between hydration shell waters were used to compute dCp for these solutes. For all solutes the dCp is significantly more positive than predicted from accessible surface area (ASA) models of heat capacity. In ASA models, nitrogen, oxygen, and phosphorus atoms are considered as uniformly polar, therefore making a negative contribution to dCp. However, the simulations show that many of these polar atoms are hydrated by water whose hydrogen bonds are less distorted than in bulk, leading to a positive dCp. This is in contrast to the effect of polar groups seen previously in small molecules and amino acids, which increase the water H-bond distortion, giving negative dCp contributions. Our results imply that dCp accompanying DNA dehydration in DNA-ligand and DNA-protein binding reactions may be significantly more negative than previously believed and that dehydration is a significant contributor to the large decrease in heat capacity seen in experiments.