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.

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A variety of synthetic modified nucleobases have been used to investigate the structure and function of RNA and DNA or act as enzyme inhibitors. A set of these modifications involves the addition or removal of a nitrogen atom in the ring. These aza and deaza modifications have garnered interest as useful biochemical tools, but information on some of their physical characteristics is lacking. In this study, the B3LYP density functional with the 6-31+G(d,p) basis set and an implicit–explicit solvent model was used to perform ab initio quantum mechanical studies to estimate p K a values of aza- and deaza-modified nucleobases. A comparison between theoretical and known experimental p K a values was carried out, and adjustment factors were applied to 57 p K a values in the purine and pyrimidine data sets.

Obscurin (720-900 kD) is a giant sarcomeric signaling protein that plays a crucial role in the arrangement of the basic contractile unit of muscle. Mutations to Obscurin and to Obscurin binding partners have been linked to human muscle diseases such as hypertrophic cardiomyopathies and muscular dystrophy. These diseases likely occur due to the rescindment of specific molecular interactions necessary for suitable function. The modular arrangement of the independently folding domains of Obscurin allows for select analysis of each of these independent binding events. Here, we present the high-resolution crystal structure of the Obscurin Ig2 domain. This region binds to the extreme Cterminus of MBPC-slow variant, although how it does this is unknown. This structure is a canonical Ig-like fold, consisting of two beta sheets coming together to form a beta sandwich.

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