Free-Energy Calculation of Ribonucleic Inosines and Its Application to Nearest-Neighbor Parameters
Free-Energy Calculation of Ribonucleic Inosines and Its Application to Nearest-Neighbor Parameters
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核糖核肌苷的自由能计算及其在最近邻参数中的应用
DOI：
10.1021/acs.jctc.0c00270
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发表时间：
2020
影响因子：
5.5
通讯作者：
Asai Kiyoshi
中科院分区：
文献类型：
--
作者：
Sakuraba Shun;Iwakiri Junichi;Hamada Michiaki;Kameda Tomoshi;Tsuji Genichiro;Kimura Yasuaki;Abe Hiroshi;Asai Kiyoshi
目前的模拟能否定量预测核糖核酸(RNA)的稳定性？在这项研究中，我们应用了含有肌苷的RNA的自由能微扰模拟，肌苷是一种改进的核糖核酸碱，用于推导RNA最近邻参数。仅用30个模拟得到的参数集来预测RNA双链的自由能差，平均无偏误差为0.70kcal/mol，这与用25个实验得到的参数得到的精度相当。我们进一步表明，将模拟得到的自由能差与实验测量的自由能差结合起来，可以将误差降低到0.60千卡/摩尔。该协议可以作为一种通用的方法来推导具有各种修改的碱基的RNA的最近邻参数。
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.