Nearest-neighbor parameter for inosine-cytosine pairs through a combined experimental and computational approach

Abstract

In RNA secondary structure prediction, nearest-neighbor parameters are used to determine the stability of a given structure. We derived the nearest-neighbor parameters for RNAs containing inosine-cytosine pairs. For parameter derivation, we developed a method that combines UV adsorption measurement experiments with free-energy calculations using molecular dynamics simulations. The method provides fast drop-in parameters for modified bases. Derived parameters were compared and found to be consistent with existing parameters for canonical RNAs. A duplex with an internal inosine-cytosine pair is 0.9 kcal/mol more unstable than the same duplex with an internal guanine-cytosine pair, and is as stable as the one with an internal adenine-uracil pair (only 0.1 kcal/mol more stable) on average.