Free-Energy Calculation of Ribonucleic Inosines and Its Application to Nearest-Neighbor Parameters

Shun Sakuraba, Junichi Iwakiri, Michiaki Hamada, Tomoshi Kameda, Genichiro Tsuji, Yasuaki Kimura, Hiroshi Abe, Kiyoshi Asai

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)5923-5935
Number of pages13
JournalJournal of chemical theory and computation
Volume16
Issue number9
DOIs
Publication statusPublished - 2020 Sep 8

ASJC Scopus subject areas

  • Computer Science Applications
  • Physical and Theoretical Chemistry

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