Calculations of pKa 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.

Automated summary

Modified nucleobases play essential structural and biological roles in RNA, but their characteristics are still poorly understood. This study determined the pK(a) values of modified nucleobases using ab initio quantum mechanical calculations, providing insights into their structural and energetic impacts within nucleic acids.