@misc{oai:repo.qst.go.jp:00073189,
 author = {Sakuraba, Shun and Iwakiri, Junichi and Hamada, Michiaki and Kameda, Tomoshi and Tsuji, Genichiro and Kimura, Yasuaki and Abe, Hiroshi and Asai, Kiyoshi and 櫻庭 俊},
 month = {Mar},
 note = {Recent advances in the RNA sequencing technology revealed that not only tRNAs but many mRNAs are chemically modified, e.g. deaminated, methylated or hydroxymethylated, in living cells. Furthermore, several evidences indicate that the RNA secondary structure change induced by the modification is deeply connected to the gene function. However, the structure prediction of the modified RNAs is difficult because the fundamental parameters to predict the structure are undetermined. Current RNA structure prediction model is built upon the nearest-neighbor model, which represents the score (energy) of the secondary structure as the sum of energies ("nearest-neighbor parameters") per two neighboring base pairs. These nearest-neighbor parameters are derived from the free-energy differences upon RNA duplex formation, which are typically determined from the UV adsorption measurements. Determining nearest neighbor parameters containing one modified RNA requires  ca. 20  UV adsorption measurements. The cost for the synthesis of modified RNA sequences makes this approach difficult to scale with various RNA modifications.

We developed a method that estimates the nearest neighbor parameters by combining the molecular dynamics (MD) simulation with the UV adsorption experiments. The free-energy differences were estimated in MD through free-energy perturbation method. The results were combined with the UV adsorption measurements to compensate the biases between the simulation and the experiment. With the new method, the required number of experiments to determine the parameters can be greatly reduced. We applied the method to estimate the nearest neighbor parameter containing inosine-cytosine pairs. The derived free-energy parameters were consistent to the parameters of canonical RNAs. Comparison to the recently reported inosine-containing nearest neighbor parameters from experiments (Wright et al., 2018) will also be discussed., Annual Meeting of the Biophysical Society},
 title = {RNA nearest-neighbor parameters for inosine-cytosine pairs derived from a combined experiment-simulation approach},
 year = {2019}
}