Nearest-neighbor parameters for 7-deaza-adenosine·uridine base pairs in RNA duplexes

Abstract

One of the major limitations in RNA structure prediction is the lack of information about the effect of nonstandard nucleotides on stability. The nonstandard nucleotide 7-deaza-adenosine (7DA) is a naturally occurring analog of adenosine that has been studied for medicinal purposes and is commonly referred to as tubercidin. In 7DA, the nitrogen in the 7 position of adenosine is replaced by a carbon. Differences in RNA duplex stability due to the removal of this nitrogen can be attributed to a possible change in hydration and a difference in base stacking interactions resulting from changes in the electrostatics of the ring. In order to determine how 7DA affects the stability of RNA, optical melting experiments were conducted on RNA duplexes that contain either internal or terminal 7DA·U pairs with all possible nearest-neighbor combinations. On average, duplexes containing 7DA·U pairs are 0.43 and 0.07 kcal/mol less stable than what is predicted for the same duplex containing internal and terminal A-U pairs, respectively. Thermodynamic parameters for all nearest-neighbor combinations of 7DA·U pairs were derived from the data. These parameters can be used to more accurately predict the secondary structure and stability of RNA duplexes containing 7DA·U pairs.

Integrating Five Feature Types Extracted From Ultrasonograms to Improve the Prediction of Thyroid Papillary Carcinoma

“…The classifier Gaussian naïve Bayes (NBayes) was utilized to build the binary prediction model [26], [27]. K nearest neighbor (KNN) algorithm was a simple but powerful classifier that relied on the definition of the inter-sample distance [28], [29]. The support vector machine (SVM) was another widely-used classifier and has been used in various types of applications, e.g., genomics [30] and fMRI imaging data [31].…”

Calculated pKa Values for a Series of Aza- and Deaza-Modified Nucleobases

“…An important characteristic of a nucleic acid is its acid–base properties, which can dictate both intra- and intermolecular interactions. − Each nucleobase within RNA or DNA has unique hydrogen-bond donor and acceptor capabilities due to its chemical composition and influences of the neighboring nucleotides. − The p K a values of the acceptor and donor pairs influence the hydrogen-bonding strength, which could impact the stability of nucleotide pairs within RNA or DNA structures. ,, Naturally occurring modifications have been reported to shift the p K a values of nucleobases by as much as 3 p K a units . The use of RNA modifications as probes for higher-order structures could therefore have unintended effects on global or local RNA folding if the nucleobase p K a values are altered.…”