Developing an Updated Strategy for Estimating the Free-Energy Parameters in RNA Duplexes

• Published in: International journal of molecular sciences Vol. 22; no. 18; p. 9708
• Main Authors: Dawson, Wayne K., Shino, Amiu, Kawai, Gota, Morishita, Ella Czarina
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 08-09-2021; MDPI
• Subjects: Benchmarks; cross-linking entropy; Energy; Free energy; free-energy parameters; genetic algorithm; Genetic algorithms; Gibbs free energy; gradient-descent fitting program; Kuhn length; Melt temperature; Monte Carlo simulation; RNA secondary structure; Transfer RNA
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22189708

For the last 20 years, it has been common lore that the free energy of RNA duplexes formed from canonical Watson–Crick base pairs (bps) can be largely approximated with dinucleotide bp parameters and a few simple corrective constants that are duplex independent. Additionally, the standard benchmark set of duplexes used to generate the parameters were GC-rich in the shorter duplexes and AU-rich in the longer duplexes, and the length of the majority of the duplexes ranged between 6 and 8 bps. We were curious if other models would generate similar results and whether adding longer duplexes of 17 bps would affect the conclusions. We developed a gradient-descent fitting program for obtaining free-energy parameters—the changes in Gibbs free energy (ΔG), enthalpy (ΔH), and entropy (ΔS), and the melting temperature (Tm)—directly from the experimental melting curves. Using gradient descent and a genetic algorithm, the duplex melting results were combined with the standard benchmark data to obtain bp parameters. Both the standard (Turner) model and a new model that includes length-dependent terms were tested. Both models could fit the standard benchmark data; however, the new model could handle longer sequences better. We developed an updated strategy for fitting the duplex melting data.