TY - JOUR
T1 - Free-Energy Calculation of Ribonucleic Inosines and Its Application to Nearest-Neighbor Parameters
AU - Sakuraba, Shun
AU - Iwakiri, Junichi
AU - Hamada, Michiaki
AU - Kameda, Tomoshi
AU - Tsuji, Genichiro
AU - Kimura, Yasuaki
AU - Abe, Hiroshi
AU - Asai, Kiyoshi
N1 - Funding Information:
The computations were performed using computing resources at ACCMS, Kyoto University, Japan, and at the Research Center for Computational Science, Okazaki, Japan. This work was supported by JSPS KAKENHI Grant Numbers 16H02484 to S.S., M.H., T.K., H.A., and K.A., 16K17778 to S.S., and 16K16143 to J.I., and by MEXT Grants-in-Aid for Scientific Research on Innovative Areas 19H05410 to S.S. and 16H06279 to K.A.
PY - 2020/9/8
Y1 - 2020/9/8
N2 - Can current simulations quantitatively predict the stability of ribonucleic acids (RNAs)? In this research, we apply a free-energy perturbation simulation of RNAs containing inosine, a modified ribonucleic base, to the derivation of RNA nearest-neighbor parameters. A parameter set derived solely from 30 simulations was used to predict the free-energy difference of the RNA duplex with a mean unbiased error of 0.70 kcal/mol, which is a level of accuracy comparable to that obtained with parameters derived from 25 experiments. We further show that the error can be lowered to 0.60 kcal/mol by combining the simulation-derived free-energy differences with experimentally measured differences. This protocol can be used as a versatile method for deriving nearest-neighbor parameters of RNAs with various modified bases.
AB - Can current simulations quantitatively predict the stability of ribonucleic acids (RNAs)? In this research, we apply a free-energy perturbation simulation of RNAs containing inosine, a modified ribonucleic base, to the derivation of RNA nearest-neighbor parameters. A parameter set derived solely from 30 simulations was used to predict the free-energy difference of the RNA duplex with a mean unbiased error of 0.70 kcal/mol, which is a level of accuracy comparable to that obtained with parameters derived from 25 experiments. We further show that the error can be lowered to 0.60 kcal/mol by combining the simulation-derived free-energy differences with experimentally measured differences. This protocol can be used as a versatile method for deriving nearest-neighbor parameters of RNAs with various modified bases.
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U2 - 10.1021/acs.jctc.0c00270
DO - 10.1021/acs.jctc.0c00270
M3 - Article
C2 - 32786906
AN - SCOPUS:85090510468
VL - 16
SP - 5923
EP - 5935
JO - Journal of Chemical Theory and Computation
JF - Journal of Chemical Theory and Computation
SN - 1549-9618
IS - 9
ER -