Calculations of pK_a Values for a Series of Naturally Occurring Modified Nucleobases

Modified nucleobases are found in functionally important regions of RNA and are often responsible for essential structural roles. Many of these nucleobase modifications are dynamically regulated in nature, with each modification having a different biological role in RNA. Despite the high abundance of modifications, many of their characteristics are still poorly understood. One important property of a nucleobase is its pK_a value, which has been widely studied for unmodified nucleobases, but not for the modified versions. In this study, the pK_a values of modified nucleobases were determined by performing ab initio quantum mechanical calculations using a B3LYP density functional with the 6-31+G(d,p) basis set and a combination of implicit-explicit solvation systems. This method, which was previously employed to determine the pK_a values of unmodified nucleobases, is applicable to a variety of modified nucleobases. Comparisons of the pK_a values of modified nucleobases give insight into their structural and energetic impacts within nucleic acids.